LncRNA-Regulated Autophagy and its Potential Role in Drug-induced Liver Injury

array:24 ["pii" => "S1665268119301929" "issn" => "16652681" "doi" => "10.5604/01.3001.0011.7381" "estado" => "S300" "fechaPublicacion" => "2018-05-01" "aid" => "70049" "copyright" => "Fundación Clínica Médica Sur, A.C." "copyrightAnyo" => "2018" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2018;17:355-63" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 150 "formatos" => array:3 [ "EPUB" => 16 "HTML" => 96 "PDF" => 38 ] ] "itemSiguiente" => array:19 [ "pii" => "S1665268119301930" "issn" => "16652681" "doi" => "10.5604/01.3001.0011.7382" "estado" => "S300" "fechaPublicacion" => "2018-05-01" "aid" => "70050" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2018;17:364-91" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 196 "formatos" => array:3 [ "EPUB" => 10 "HTML" => 114 "PDF" => 72 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Association Between Hepatitis C Virus and Chronic Kidney Disease: A Systematic Review and Meta-Analysis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "364" "paginaFinal" => "391" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 344 "Ancho" => 509 "Tamanyo" => 15228 ] ] "descripcion" => array:1 [ "en" => "aHR and 95% confidence intervals for each study (n = 15 longitudinal studies; n = 2,299,134 unique patients) (Outcome: incidence of CKD). aHR of CKD associated with HCV (longitudinal surveys), 1.54 (95% CI, 1,26; 1.87) (P < 0.001). Q value by χ2 test, 500.3 (P = 0.0001), I2 = 97.2%" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Fabrizio Fabrizi, Francesca M. Donato, Piergiorgio Messa" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Fabrizio" "apellidos" => "Fabrizi" ] 1 => array:2 [ "nombre" => "Francesca M." "apellidos" => "Donato" ] 2 => array:2 [ "nombre" => "Piergiorgio" "apellidos" => "Messa" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119301930?idApp=UINPBA00004N" "url" => "/16652681/0000001700000003/v1_201905160920/S1665268119301930/v1_201905160920/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119301917" "issn" => "16652681" "doi" => "10.5604/01.3001.0011.7380" "estado" => "S300" "fechaPublicacion" => "2018-05-01" "aid" => "70048" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2018;17:345-54" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 401 "formatos" => array:3 [ "EPUB" => 17 "HTML" => 278 "PDF" => 106 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Non-Alcoholic Fatty Liver Disease in Children and Adolescents: Lifestyle Change - a Systematic Review and Meta-Analysis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "345" "paginaFinal" => "354" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 3." "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 434 "Ancho" => 669 "Tamanyo" => 70539 ] ] "descripcion" => array:1 [ "en" => "Combined effect of the intervention on ALT levels." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Melina Utz-Melere, Cristina Targa-Ferreira, Bernardo Lessa-Horta, Matias Epifanio, Marialena Mouzaki, Angelo A. Mattos" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Melina" "apellidos" => "Utz-Melere" ] 1 => array:2 [ "nombre" => "Cristina" "apellidos" => "Targa-Ferreira" ] 2 => array:2 [ "nombre" => "Bernardo" "apellidos" => "Lessa-Horta" ] 3 => array:2 [ "nombre" => "Matias" "apellidos" => "Epifanio" ] 4 => array:2 [ "nombre" => "Marialena" "apellidos" => "Mouzaki" ] 5 => array:2 [ "nombre" => "Angelo A." "apellidos" => "Mattos" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119301917?idApp=UINPBA00004N" "url" => "/16652681/0000001700000003/v1_201905160920/S1665268119301917/v1_201905160920/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "titulo" => "LncRNA-Regulated Autophagy and its Potential Role in Drug-induced Liver Injury" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "355" "paginaFinal" => "363" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Juan Zhou, Yi Li, XinYu Liu, Yunzhu Long, Jun Chen" "autores" => array:5 [ 0 => array:3 [ "nombre" => "Juan" "apellidos" => "Zhou" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "**" "identificador" => "aff0010" ] ] ] 1 => array:3 [ "nombre" => "Yi" "apellidos" => "Li" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "XinYu" "apellidos" => "Liu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Yunzhu" "apellidos" => "Long" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "**" "identificador" => "aff0010" ] ] ] 4 => array:4 [ "nombre" => "Jun" "apellidos" => "Chen" "email" => array:1 [ 0 => "chenjun66@csu.edu.cn" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Liver Diseases Center, Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China" "etiqueta" => "*" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Infectious Diseases, The affiliated Zhuzhou Hospital Xiangya Medical college, Central South University, Zhuzhou, Hunan, P.R. China" "etiqueta" => "**" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "*" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 426 "Ancho" => 696 "Tamanyo" => 64126 ] ] "descripcion" => array:1 [ "en" => "ATGs involved in the initiation of autophagy induced by endoplasmic reticulum (ER) stress. First, the ULK1-ATG13-FIP200-ATG101 complex is activated. Then, PtdIns3K class III complexes (Beclin1-VPS15-VPS34) are induced to transform phosphatidylinositol 3-phosphate (PtdIns3P) intensified by ATG14, followed by recruitment of downstream effectors such as DFCP1 and WIPI-family. ATG12-ATG5-ATG16L1 complex exerts its E3-like function and thus catalyzes LC3-I, leading to LC3 cleavage by ATG4 to LC3-II." ] ] ] "textoCompleto" => "IntroductionDrug-induced liver injury (DILI) has gained significant attention worldwide in the last decades on account of its significant morbidity and mortality.<a class="elsevierStyleCrossRefs" href="#bib0005">1</a>–<a class="elsevierStyleCrossRef" href="#bib0020">4</a> It is one of the most common causes of acute liver failure to date in the United States and Europe, and a leading reason for emergent liver transplant.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>,<a class="elsevierStyleCrossRef" href="#bib0030">6</a> Further understanding of the pathogenesis of DILI might have important value for preventing and treating the disease. The pathogenesis of drug-induced hepatitis is considerably complex, involving multiple pathological processes, such as liver cell damage, intracellular fat change, fibrosis, apoptosis, necrosis, and so on.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> Although the pattern of DILI can be generalized as intrinsic types referring to drugs with dose-dependent and idiosyncratic types characterizing by an adaptive immune attack,<a class="elsevierStyleCrossRef" href="#bib0040">8</a> the common downstream events were the imbalance between pathways to injury and restorative tissue repair.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> It is related to not only the type and nature of the drug, but also the genetic background of the individual. However, the ultimate common pathway is the activation of the cell death signal.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>,<a class="elsevierStyleCrossRef" href="#bib0055">11</a> Results from a genomics approach revealed that endoplasmic reticulum (ER) stress and nuclear factor-erythroid 2-related factor 2 (Nrf2)signaling are two major pathways involved in DILI. Other is subsequent protein kinase R-like ER kinase (PERK), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) activation, which may be the crosstalk with pro-apoptosis signaling.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> It is supported by the research on CHOP knockout (KO) mice that can protect liver cells from APAP-induced damage and reduce necrosis, exhibiting proliferation and increased hepatocyte survival.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> Therefore, ER stress, which has dual effects either cause apoptosis or protective effect, is the key process in the pathogenesis of DILI. In neurons, ATF5 upregulation induced mainly by ER stress does not lead to apoptosis, implicating that ER stress acts as a prosurvival mechanism.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> Moreover, inhibition of IRE1a followed by ER stress enhances the cytotoxic effects.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> The role of ER stress in promoting cell survival and death is still unknown. Therefore, this review focused on the molecular mechanism of autophagy referring to restorative tissue repair regulated by long noncoding RNA (lncRNA) for a better understanding of the pathogenesis, diagnosis, and treatment of DILI.Autophagy and DiliAutophagy is a process designed to sequester and degrade intracellular components, beginning with the formation of double-membrane vesicles tightly controlled by the autophagy-related genes (ATG). It is a critical adaptive response for cell survival, which can be dramatically induced by starvation and a broad range of stressors, such as ER stress, pathogen infection, oxidative stress, and so on.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> The failure to get rid of intracellular wastes by autophagy greatly disrupts homeostasis, which can invariably induce cell death and inflammation consequently resulting in tissue injury. Autophagy acts as an intracellular degradation process associated with lysosomes. It mainly targets cy-tosolic components such as abnormal proteins and or-ganelles.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> It is essentially a self-repairing process to deal with potential risk factors for intracellular physiological processes and prolong the life of cells via energy regeneration<a class="elsevierStyleCrossRef" href="#bib0090">18</a>,<a class="elsevierStyleCrossRef" href="#bib0095">19</a> and removal of harmful or useless substances. Otherwise, apoptosis can sequentially be elicited as another protective factor to relieve stress when autophagy fails to perform its functions.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> So far, more than 40 autophagy-related genes have been identified in yeast and mammals, which tightly control the intracellular adaptive process via multiple signaling pathways.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> A total of 15 core ATG genes (ATG1-10, 12-14, 16, and 18), which are highly conserved in mammals, are required for selective autophagy for protein aggregates, damaged mitochondria, excessive peroxisomes, ribosomes, and invading pathogens. The expression and regulation of these genes are closely related to the death pathway.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>,<a class="elsevierStyleCrossRef" href="#bib0110">22</a>The hepatocytes have a higher capacity for autophagy compared with other cell types because of a large number of ER, mitochondria, and lysosomal enzymes required for multiple metabolic functions and to cope with different biological or chemical stimuli, ultimately ensuring cellular homeostasis.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>,<a class="elsevierStyleCrossRef" href="#bib0120">24</a> The ER is one of the main sites for drug metabolism in the liver, and also the assembly and modification of secretory and integral membrane proteins. ER stress is the stimulus for autophagy. Further, ER is the initiation site for the biogenesis of autophago-somes.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>,<a class="elsevierStyleCrossRef" href="#bib0115">23</a> ER stress and autophagy are related to apoptosis and hence have been recognized as critical pathways in the regulation of cell death.<a class="elsevierStyleCrossRef" href="#bib0120">24</a>,<a class="elsevierStyleCrossRef" href="#bib0125">25</a> Recent studies have demonstrated essential protective functions of autophagy in hepatocytes during liver injury.<a class="elsevierStyleCrossRef" href="#bib0075">15</a>,<a class="elsevierStyleCrossRefs" href="#bib0130">26</a>–<a class="elsevierStyleCrossRef" href="#bib0170">34</a> Thymidine analogs were found to inhibit autophagy on constitutive and induced levels in hepatocytes, increasing reactive oxygen species production, lipid accumulation, and hepatic dysfunction, and thereby resulting in apoptosis.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> Doxorubicin, an antibiotic drug used for chemotherapy in various cancers, induces cardiotoxicity, which is consistent with dysregulated autophagy and autophagosome formation shown by a variety of approaches in cardiomyocytes.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> Knockout of ATG5 the autophagy gene has confirmed that deficiency of autophagy can increase acute liver injury induced by D-galactosamine/lipopolysaccharides in mice. Similar results were observed with a knockout of the gene Atg7, leading to liver injury with a hepatocyte-specific loss of autophagy.<a class="elsevierStyleCrossRef" href="#bib0160">32</a>,<a class="elsevierStyleCrossRef" href="#bib0175">35</a> Deletion of the autophagy gene Atg7 led to the accumulation of concentric membranous structures, which were continuous with the rough ER. These structures were surrounded by various aberrant mitochondria and lipid droplets. Disorganized hepatic lobules and cell swelling were noted on histological analysis, while no hepatocyte proliferation or regeneration was observed. These findings were consistent with the protective role of autophagy in eliminating abnormal organelles for maintaining normal liver metabolism.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> ER is an original site for autophagy. Moreover, autophagy closely related to ER is essential in protecting the hepatocytes from damage in metabolic processes.Drug metabolism in hepatocytes primarily occurs on ER. Hence, accumulation of reactive metabolites and conjugate proteins can strikingly increase the ER stress in response to overdose or long-term use of drugs.<a class="elsevierStyleCrossRefs" href="#bib0185">37</a>–<a class="elsevierStyleCrossRef" href="#bib0195">39</a> ER stress is resolved by the activation of the unfolded protein response, which can be elicited by three stress sensors inositol-requiring protein 1α, activating transcription factor 6, and protein kinase RNA-like ER kinase to orchestrate the normal ER function.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> The collaboration of these processes helps in deciding the scale of adaptive capacity and thus governs whether cells will re-establish homeostasis or activate cell death programs via an internal pathway of apoptosis with inhibition of autophagy.<a class="elsevierStyleCrossRef" href="#bib0205">41</a> Existing data implicated that autophagy, as a downstream mediator of ER stress, had a pronounced decrease in cell viability during drug-induced damage of rat hepatocytes.<a class="elsevierStyleCrossRef" href="#bib0210">42</a> The mechanism underlying hepatotoxicity caused by drugs has not been recognized yet. However, it seems that these mechanisms are closely related to the increase in damaged organelles and nonfunctional proteins during biotransformation to metabolites, resulting in increasing ER stress and oxidative stress. For instance, acetaminophen (APAP), which is widely used as an antipyretic and analgesic drug, is the most common source of severe hepatotoxicity. APAP-induced hepatotoxicity has been demonstrated to be mediated mainly via its reactive metabolite. During APAP overdose, N-acetyl-p-benzo-quinone imine (NAPQI), which is generated from APAP metabolism by cytochrome P450, can deplete hepatic stores of glutathione, interfering with cellular redox homeostasis.<a class="elsevierStyleCrossRef" href="#bib0215">43</a>,<a class="elsevierStyleCrossRef" href="#bib0220">44</a> The remaining NAPQI reacts with many cellular proteins and induces autophagy acting as an adaptive response to remove damaged organelles, especially mitochondria. Furthermore, induction of autophagy inhibited APAP-induced hepatotoxicity, preventing against liver injury.<a class="elsevierStyleCrossRef" href="#bib0225">45</a>,<a class="elsevierStyleCrossRef" href="#bib0230">46</a> In addition to ER stress, NRF2-mediated oxidative stress response has implicated in DILI, which suggested excessive reactive oxygen species (ROS) were generated by the oxidative metabolism of drugs.<a class="elsevierStyleCrossRef" href="#bib0235">47</a> It is generally believed that ROS result from both the NAD(P)H oxidase (NOX) and CYP450 system using co-factor NADPH, which is following by the oxidative damage mainly manifested as lipid peroxidation.<a class="elsevierStyleCrossRef" href="#bib0240">48</a> However, ROS generation can be largely attributed to a NOX activity rather than the CYP450 system when incubated acetaminophen and NADPH in microsomes of rat liver.<a class="elsevierStyleCrossRef" href="#bib0245">49</a> The recent development indicated that autophagy-deficient caused oxidative stress increasing in melanocytes, also the upregulation of ROS, Nrf2 antioxidant signaling and lipid oxidation.<a class="elsevierStyleCrossRef" href="#bib0250">50</a> Whether these phenomena existing in hepato-cytes need further experiments to prove. Although the hepatocyte damage induced by different drugs may have varied pathways, the central factors are the reactive metabolites, resulting in abnormal proteins or organelles interfering with the normal physiological program. This provides the framework for thinking about ER stress-induced autophagy, which is a cellular adaptive response to cope with these stresses involved in liver injury caused by drugs. Researchers suggested ER stress and au-tophagy can constitute an effective defense mechanism against multiple insult from lipid metabolism, alcohol and non-alcoholic fatty liver in hepatocytes which may be similar to DILI.<a class="elsevierStyleCrossRef" href="#bib0255">51</a> It has been proven autophagy-enhancing drugs can alleviate liver steatosis, liver injury, and dyslip-idemia in both alcohol-fed and HFD(high fat diet)-fed mice,<a class="elsevierStyleCrossRef" href="#bib0260">52</a> yet it is not clear how autophagy is initiated in these contexts that may be different from DILI. Further studies to clarify the intensity of autophagy induced by ER stress, particularly originating from drug biotransformation in hepatocytes, might provide important information on DILI.Regulation of AutophagyThe performance of autophagy includes two steps: formation of autophagosomes and generation of autolyso-somes from the fusion of double-membrane vesicles with lysosomes.<a class="elsevierStyleCrossRef" href="#bib0265">53</a> The autophagosomal membrane originates from the ER,<a class="elsevierStyleCrossRef" href="#bib0270">54</a> as confirmed by two groups that demon-strated the physical connection between the ER and isolation membrane using 3D electron microscopy.<a class="elsevierStyleCrossRef" href="#bib0275">55</a>,<a class="elsevierStyleCrossRef" href="#bib0280">56</a>So far, three critical protein complexes have been identified, including the ULK1-ATG13-FIP200-ATG101 complex, the Beclin1-ATG14-Vps34-Vps15 (class III PI3-kinase) complex, and the ATG12-ATG5-ATG16L1 complex. The ULK1 complex appears to be the most upstream unit, followed by ATG14-containing PI3-kinase complex, which together regulate the formation of both DFCP1 and WIPI-1 structures. Most downstream events are activation of the ATG12 system and the LC3<a class="elsevierStyleCrossRef" href="#bib0285">57</a> (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>). These proteins participate in different steps of autophagy in a temporal order based on their roles in autophagosome formation and are regulated by each other through diverse pathways relying on different intracellular stimuli or different cell types.<a class="elsevierStyleCrossRef" href="#bib0290">58</a> Therefore, regulation of autophagy involves not only the interaction between the core ATG proteins but also variation in ATG genes at the transcrip-tional and posttranslational levels.<a class="elsevierStyleCrossRef" href="#bib0250">50</a> Autophagy occurs at a constitutive basal level but can be upregulated by different types of stresses such as starvation, damaged intracellular components, or pathogen infection.<a class="elsevierStyleCrossRef" href="#bib0295">59</a> It first involves the recruitment and co-working of core ATG proteins,<a class="elsevierStyleCrossRef" href="#bib0300">60</a> followed by changes at the transcriptional and post-tran-scriptional levels,<a class="elsevierStyleCrossRef" href="#bib0290">58</a> which probably govern the extent of autophagy to cope with a strong or prolonged stimulus.<elsevierMultimedia ident="f0005"></elsevierMultimedia>Recent progresses in autophagy research in genetically modified mice (especially the study on Atg5 KO mice) have revealed the important role of some ATG genes, indicating the importance of autophagy for survival.<a class="elsevierStyleCrossRef" href="#bib0305">61</a> Other four phenotypes of Atg7, Atg9, and Atg16L1 have shown a result similar to that in Atg5 using the gene KO mice model. Atg5, Atg7, Atg9, Atg16L1, Beclin 1, and FIP200 are indispensable components for the formation of autophagosomes,<a class="elsevierStyleCrossRef" href="#bib0310">62</a> implying the involvement of these proteins in the regulation of autophagy. In line with these findings, the expression of ATG3, ATG5, ATG12, ULK1, LC3B, Beclin-1, and GABA(A)receptor-associated protein like 1 was downregulated in human osteoarthritis cartilage compared with the normal cartilage, whereas the expression of mTOR was significantly upregulated. The expression levels of these proteins could be subsequently restored on deleting mTOR gene in the cartilage of mice.<a class="elsevierStyleCrossRef" href="#bib0315">63</a> The involvement of ATG5, ATG7, ATG9, and ATG16L in the conjugation system, which directly participates in the formation of phosphatidylethanolamine with the expansion of autophagosomes (<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>),<a class="elsevierStyleCrossRef" href="#bib0300">60</a> suggests that the intermediate stage presumably is vital in regulating the extent of autophagy. For instance, an inhibitor of soluble epoxide hydrolase can recover the levels of Atg12-Atg5 and LC3-II conjugates, resulting in the upregulation of hepatic autophagy to modulate inflammation in fat-1 mice.<a class="elsevierStyleCrossRef" href="#bib0320">64</a> Also, deletion of Atg5 in hepatocytes can lead to loss of au tophagy, consequently increasing apoptosis, inflammation, and fibrosis.<a class="elsevierStyleCrossRef" href="#bib0325">65</a> During prolonged starvation, the expression level of SQSTM1/p62, a substrate protein degraded by autophagy, is determined by three factors: reduction in au-tophagic degradation, activation of transcriptional factors, and availability of amino acids needed to synthesize new proteins.<a class="elsevierStyleCrossRef" href="#bib0315">63</a><elsevierMultimedia ident="f0010"></elsevierMultimedia>Other substrates involved in autophagy might have similar regulatory processes. A study on the transcriptional regulation of autophagy revealed that the fed-state sensing nuclear receptor inhibited autophagy by binding to 178 (of 230) autophagy-related genes for decreasing their expression, and CREB (the fasting transcriptional activator) promoted autophagic degradation of lipids via upregulating 112 genes under nutrient-deprived conditions in mouse liver.<a class="elsevierStyleCrossRef" href="#bib0330">66</a>These signaling pathways and transcriptional or post-transcriptional factors manipulate autophagy and serve as critical components to dispose of stress or changes in the liver.<a class="elsevierStyleCrossRef" href="#bib0120">24</a>Ample evidence indicates different classes of RNA, ranging from small to long noncoding RNAs, as key regulators of gene expression.<a class="elsevierStyleCrossRef" href="#bib0335">67</a> In a hepatocyte dedifferentiation study, massive alterations of noncoding transcriptome were found, hallmarked by increased expression of small nucleolar RNAs, lncRNAs, microRNAs (miRNAs), and ribosomal genes, preceding changes in protein-coding genes. Notably, only the regulation of lncRNAs among the ncRNAs displayed significant temporal and directional congruity with the profiles of coding genes. This showed that lncRNA primarily took part in regulating the expression of coding genes, influencing protein output. On the contrary, lncRNA might be generated from the transcription of protein-coding genes.<a class="elsevierStyleCrossRef" href="#bib0340">68</a> Above all, it is reasonable to speculate that the regulation of the transcription of ATG was partially manipulated by lncRNA. Therefore, an in-depth understanding of the molecular mechanisms underlying the manipulation of autophagy is crucial to obtain new insights on the strategies of diagnosing and treating autophagy-associated liver diseases.IncRNA-regulated autophagyLncRNA (length > 200 bases) have attracted the attention of many researchers recently because of their involvement in diverse fundamental processes, in particular gene expression, which refers to recruiting chromatin-modify-ing complexes, enhancing transcription, decoying miR-NAs, providing a scaffold, and encoding peptides.<a class="elsevierStyleCrossRef" href="#bib0345">69</a>,<a class="elsevierStyleCrossRef" href="#bib0350">70</a>A study on the evolutionary history of lncRNA revealed that lncRNA promoters were more frequently associated with transcription factors compared with random intergenic regions, suggesting their potential role in tran-scription.<a class="elsevierStyleCrossRef" href="#bib0355">71</a> MiRNA has always been considered as the central player in controlling gene expression at the post-transcriptional level.<a class="elsevierStyleCrossRef" href="#bib0360">72</a> It has been extensively studied as a repressor of gene expression or cleavage of mRNA.<a class="elsevierStyleCrossRef" href="#bib0090">18</a>,<a class="elsevierStyleCrossRef" href="#bib0255">51</a>,<a class="elsevierStyleCrossRef" href="#bib0365">73</a> During the last decade, increasing evidence has indicated that lncRNA with low or no protein-coding potential may be equally important in the regulation of gene expression.<a class="elsevierStyleCrossRef" href="#bib0370">74</a> A large number of studies have confirmed the role of lncRNA in diverse biological functions via different mechanisms, including regulating the expression of adjoining protein,<a class="elsevierStyleCrossRef" href="#bib0375">75</a> negatively regulating RNA polymerase II (RNAP II),<a class="elsevierStyleCrossRef" href="#bib0380">76</a> and regulating alternative splicing<a class="elsevierStyleCrossRef" href="#bib0385">77</a> and microRNA sponges termed as competing endogenous RNAs (ceRNAs).<a class="elsevierStyleCrossRef" href="#bib0390">78</a> The most important function of RNA is to synthesize the proteins necessary for life activities. The interaction between different kinds of RNA, in particular ncRNA and mRNA, has a decisive role in regulating transcription and translation. After all, communication between the same kind of RNAs takes precedence over heterogeneous crosstalk. The challenge was that these experiments revealed what happened, but not the coordination in time and space. The present study paid close attention to some of the recent data concerning the involvement of lncRNA in regulating different steps of autophagy especially the expression of related proteins, giving a better understanding of the process.Some studies found that lncRNA APF (AK079427, 1695 nt long) regulates the occurrence of autophagy via inhibiting miR-188-3p in a sequence-specific manner to significantly protect the expression of ATG7 in the myocardial cells of mice.<a class="elsevierStyleCrossRef" href="#bib0395">79</a> In addition, the overexpression of lncRNA (FLJ11812, located in the 3' UTR of TGFB2 gene, contains 1370 nt) could promote autophagy by increasing the ATG13 protein level. Furthermore, FLJ11812 competes to bind with MIR4459, which targets ATG13 to down regulate its expression, which is analogous to the mechanism of APF acting as a competing endogenous RNA (ceRNA) to control ATG13 level<a class="elsevierStyleCrossRef" href="#bib0400">80</a>. LncRNA PTENP1 indirectly contributes to autophagy by effectively upregulating ULK1, ATG7, and p62 levels via the antagonizing action of miR-17 in HCC cells.<a class="elsevierStyleCrossRef" href="#bib0405">81</a> Another study confirmed that the overexpression of HOTAIR, an lncRNA that could promote the activation of autophagy in HCC cell lines, was equivalent to upregulating the expression levels of ATG3 and ATG7 (<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0410">82</a> These findings further explained the importance of the expression of the aforementioned key genes in modulating autophagy. Also, lncRNA had a strong influence on the protein expression. LncRNA has been proved to be crucial in regulating autophagy and participate in the pathophysiological processes of various human diseases, such as NBR2 and tumor development,<a class="elsevierStyleCrossRef" href="#bib0415">83</a> MEG3 and bacterial infections,<a class="elsevierStyleCrossRef" href="#bib0420">84</a> TGFB2-OT1 and in-flammation,<a class="elsevierStyleCrossRef" href="#bib0425">85</a> Risa and insulin sensitivity,<a class="elsevierStyleCrossRef" href="#bib0430">86</a> PCGEM1 and osteoarthritic synoviocytes,<a class="elsevierStyleCrossRef" href="#bib0435">87</a> and so on. The regulation network of gene expression involves lncRNA in au-tophagy, providing a new insight into the mechanism of hepatocyte injury. The liver is found to be rich in lncR-NA, followed by testes and neural tissues in the body.<a class="elsevierStyleCrossRef" href="#bib0355">71</a> Therefore, further understanding of the role of lncRNA during pathophysiological conditions can help in developing potential diagnostic and therapeutic methods for patients with DILI.<elsevierMultimedia ident="t0005"></elsevierMultimedia>ConclusionsAutophagy is the most basic protective pattern for normal physical activities and survival. Exploring the regulatory mechanism influencing the extent of autophagy at the molecular level, especially for protein transcription and translation, can substantially contribute to understanding the pathophysiology of cellular damage. While manipulating autophagy, networks between lncRNA and mRNA might be crucial for key gene expression, which might help to understand the basic pathophysiological conditions and the development of autophagy-associated DILI." "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:3 [ "identificador" => "xres1190755" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0010" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1110032" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "s0010" "titulo" => "Autophagy and Dili" ] 4 => array:3 [ "identificador" => "s0015" "titulo" => "Regulation of Autophagy" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "s0020" "titulo" => "IncRNA-regulated autophagy" ] ] ] 5 => array:2 [ "identificador" => "s0025" "titulo" => "Conclusions" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-02-11" "fechaAceptado" => "2018-03-07" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1110032" "palabras" => array:4 [ 0 => "Autophagy" 1 => "Autophagy-related genes" 2 => "Drug-induced liver injury" 3 => "Long noncoding RNA" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Introduction and aim. Autophagy and its regulated pathways participate in many important cellular physiology and pathological processes involving protein aggregates, damaged mitochondria, excessive peroxisomes, ribosomes, and invading pathogens. This study aimed to review recently published studies and further describe the long noncoding RNA (lncRNA)-regulated autophagy during drug-induced liver injury (DILI).Material and methods. DILI, autophagy, autophagy-related genes (ATGs), and lncRNA were used as key words to search published studies from PubMed, Google Scholar, and Web of Science. All related studies were reviewed and analyzed.Results. Many studies explicitly indicated that DILI and its progression to acute liver failure were causatively linked to endoplasmic reticulum stress and subsequently induced autophagy, which protect hepatocytes during DILI. LncRNA, as a noncoding RNA, influences the regulation of the expression of ATGs to manipulate autophagy.Conclusions. This review described the recent findings on autophagy and its possible lncRNA-miRNA-associated pathways, thereby providing new insights for further studies on the pathogenesis of DILI." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 426 "Ancho" => 696 "Tamanyo" => 64126 ] ] "descripcion" => array:1 [ "en" => "ATGs involved in the initiation of autophagy induced by endoplasmic reticulum (ER) stress. First, the ULK1-ATG13-FIP200-ATG101 complex is activated. Then, PtdIns3K class III complexes (Beclin1-VPS15-VPS34) are induced to transform phosphatidylinositol 3-phosphate (PtdIns3P) intensified by ATG14, followed by recruitment of downstream effectors such as DFCP1 and WIPI-family. ATG12-ATG5-ATG16L1 complex exerts its E3-like function and thus catalyzes LC3-I, leading to LC3 cleavage by ATG4 to LC3-II." ] ] 1 => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 457 "Ancho" => 696 "Tamanyo" => 32139 ] ] "descripcion" => array:1 [ "en" => "ATG12-ATG5 system involved in the expansion of autophagosomes. First, ATG7 activates ATG12 by functioning as an E1-like enzyme. Then, ATG12 conjugates to ATG5 and ATG16L, forming a functional complex as an E3-like enzyme. Meanwhile, activated ATG12 recruits ATG3, which acts as an E2-like enzyme. Finally, LC3 conjugates to PE under the action of the complex and ATG3." ] ] 2 => array:7 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">lncRNA \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Targest \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Role in autophagy \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Diseases \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">References \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MALAT1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">miR-30a miR-101 miR-216b miR-124 miR-23b-3p \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MALAT1 activates autophagy serving as a molecular sponge for miR-30a that suppresses Beclin1-dependent autophagy and miR-101, RAB5A, and ATG4D It also binds to miR-216b, modulating autophagy It promotes autophagy by directly targeting miR-124 It induces autophagy for acting as a ceRNA for miR-23b-3p to increase the expression of ATG12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ischemic stroke; glioma; hepatocellular carcinoma; retinoblastoma; gastric cancer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="right" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0440">88</a>, <a class="elsevierStyleCrossRef" href="#bib0445">89</a>, <a class="elsevierStyleCrossRef" href="#bib0450">90</a>, <a class="elsevierStyleCrossRef" href="#bib0455">91</a>, <a class="elsevierStyleCrossRef" href="#bib0460">92</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TGFB2-OT1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">miR-3960 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TGFB2-OT1 acts as a competing endogenous RNA regulating the expression of \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vascular endothelial cell \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="right" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0425">85</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(FLJ11812) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">miR-4488 miR-4459 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">the miRNA targets CERS1, NAT8L, and LARP1, which participate in autophagy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">dysfunction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">APF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">miR-188-3p \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">APF regulates the expression of ATG7 through miR-188-3p \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="right" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0465">93</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HULC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">miR-6886-3p miR-6825-5p, miR-6845-5p \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HULC downregulates miR-6825-5p, miR-6845-5p, and miR-6886-3p to protect autophagy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatocellular carcinoma (HCC) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="right" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0470">94</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AC023115.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">miR-26a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AC023115.3 acts as a competing endogenous RNA for miR-26a, which has an inhibitory effect on GSK3â leading to a decrease in autophagy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glioma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="right" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0475">95</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HNF1A-AS1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">miR-30b \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HNF1A-AS1 promotes autophagy by acting as a ceRNA for miR-30b, which can regulate the expression of Bcl-2 and ATG5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatocellular carcinoma (HCC) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="right" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0480">96</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PTENP1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">miR-17 miR-19b miR-20a \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PTENP1 induces autophagy through decoying miR-17, miR-19b, and miR-20a, which target autophagy genes as ULK1, ATG7, and p62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatocellular carcinoma (HCC) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="right" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0405">81</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PVT1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">miR-186 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PVT1 induces autophagy by targeting miR-186, which decreases the expression of Atg7 and Beclin1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glioma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="right" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0485">97</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HOTAIR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">miR-454-3p \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HOTAIR increases autophagy by inducing DNA methylation of miR-454-3p, which targets STAT3 and ATG12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chondrosarcoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="right" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0490">98</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GAS5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">miR-21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GAS5 suppresses autophagy for acting as a negative regulator of miR-21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Osteoarthritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="right" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0495">99</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PCGEM1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">miR-770 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PCGEM1 induces autophagy by acting as a sponge for miR-770 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Osteoarthritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="right" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0500">100</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2031790.png" ] ] ] ] "descripcion" => array:1 [ "en" => "IncRNA-miRNA associated with autophagy." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0010" "bibliografiaReferencia" => array:100 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug-induced liver injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5858/arpa.2014-0214-RA" "Revista" => array:6 [ "tituloSerie" => "Arch Pathol Lab Med" "fecha" => "2015" "volumen" => "139" "paginaInicial" => "876" "paginaFinal" => "887" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Teschke R, Frenzel C, Wolff A, Eickhoff A, Schulze J. Drug induced liver injury?: accuracy of diagnosis in published reports. Ann Hepatol 2014; 248-55." ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug Induced Liver Injury Network" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.27317" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2015" "volumen" => "60" "paginaInicial" => "1399" "paginaFinal" => "1408" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug Induced Liver Injury at a Tertiary Hospital in India: Etiology, Clinical Features and Predictors of Mortality" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5604/16652681.1235488" "Revista" => array:6 [ "tituloSerie" => "Ann Hepatol" "fecha" => "2017" "volumen" => "16" "paginaInicial" => "442" "paginaFinal" => "450" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug-induced liver injury: Do we know everything" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4254/wjh.v9.i10.491" "Revista" => array:6 [ "tituloSerie" => "World J Hepatol" "fecha" => "2017" "volumen" => "9" "paginaInicial" => "491" "paginaFinal" => "502" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug-induced liver injury: recent advances in diagnosis and risk assessment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gutjnl-2016-313369" "Revista" => array:6 [ "tituloSerie" => "Gut" "fecha" => "2017" "volumen" => "66" "paginaInicial" => "1154" "paginaFinal" => "1164" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug Induced Liver Injury: Review with a Focus on Genetic Factors, Tissue Diagnosis, and Treatment Options" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.14218/JCTH.2015.00007" "Revista" => array:6 [ "tituloSerie" => "J Clin Transl Hepatol" "fecha" => "2015" "volumen" => "3" "paginaInicial" => "99" "paginaFinal" => "108" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CSH guidelines for the diagnosis and treatment of drug-induced liver injury" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s12072-017-9793-2" "Revista" => array:6 [ "tituloSerie" => "Hepatol Int" "fecha" => "2017" "volumen" => "11" "paginaInicial" => "221" "paginaFinal" => "241" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ACG Clinical Guideline: The Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ajg.2014.131" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol" "fecha" => "2014" "volumen" => "109" "paginaInicial" => "950" "paginaFinal" => "966" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug-induced liver injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Med (Northfield Il)" "fecha" => "2016" "volumen" => "38" "paginaInicial" => "S44" "paginaFinal" => "S48" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "NAT2 genetic polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in Chinese community population" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Hepatol" "fecha" => "2012" "volumen" => "11" "paginaInicial" => "700" "paginaFinal" => "707" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug-Induced Endoplasmic Reticulum and Oxidative Stress Responses Independently Sensitize Toward TNFα-Mediated Hepatotoxicity" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/toxsci/kfu072" "Revista" => array:6 [ "tituloSerie" => "Toxicol Sci" "fecha" => "2014" "volumen" => "140" "paginaInicial" => "144" "paginaFinal" => "159" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CHOP is a critical regulator of acetaminophen-induced hepatotoxicity" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2013.04.024" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2013" "volumen" => "59" "paginaInicial" => "495" "paginaFinal" => "503" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protective neuronal induction of ATF5 in endoplasmic reticulum stress induced by status epilepticus" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/brain/awt044" "Revista" => array:6 [ "tituloSerie" => "Brain" "fecha" => "2013" "volumen" => "136" "paginaInicial" => "1161" "paginaFinal" => "1176" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Xie H, Tang C-HA, Song JH, Mancuso A, Valle JR Del, Cao J, Xiang Y, et al. IRE1α RNase-dependent lipid homeostasis promotes survival in Myc-transformed cancers. J Clin Invest. Published Online First: 30 January 2018." ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A current perspective of autophagosome biogenesis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/cr.2013.159" "Revista" => array:6 [ "tituloSerie" => "Cell Res" "fecha" => "2014" "volumen" => "24" "paginaInicial" => "58" "paginaFinal" => "68" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Functions of autophagy in normal and diseased liver" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4161/auto.25063" "Revista" => array:6 [ "tituloSerie" => "Autophagy" "fecha" => "2013" "volumen" => "9" "paginaInicial" => "1131" "paginaFinal" => "1158" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autophagy in the Cellular Energetic Balance" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cmet.2011.04.004" "Revista" => array:6 [ "tituloSerie" => "Cell Metab" "fecha" => "2011" "volumen" => "13" "paginaInicial" => "495" "paginaFinal" => "504" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lin Haifan. Induction of Autophagy, a Promising Approach for Treating Liver Injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrm2621" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Mol Cell Biol" "fecha" => "2009" "volumen" => "10" "paginaInicial" => "116" "paginaFinal" => "125" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhibition of macroautophagy triggers apoptosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/MCB.25.3.1025-1040.2005" "Revista" => array:6 [ "tituloSerie" => "Mol Cell Biol" "fecha" => "2005" "volumen" => "25" "paginaInicial" => "1025" "paginaFinal" => "1040" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dynamics and diversity in autophagy mechanisms: lessons from yeast" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrm2708" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Mol Cell Biol" "fecha" => "2009" "volumen" => "10" "paginaInicial" => "458" "paginaFinal" => "467" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autophagy: more than a nonselective pathway" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2012/219625" "Revista" => array:5 [ "tituloSerie" => "Int J Cell Biol" "fecha" => "2012" "volumen" => "2012" "paginaInicial" => "219625" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cathepsin L. A new proteinase from rat-liver lysosomes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Biochem" "fecha" => "1977" "volumen" => "74" "paginaInicial" => "293" "paginaFinal" => "301" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autophagy: Renovation of Cells and Tissues" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cell.2011.10.026" "Revista" => array:6 [ "tituloSerie" => "Cell" "fecha" => "2011" "volumen" => "147" "paginaInicial" => "728" "paginaFinal" => "741" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Opinion: Autophagy: dual roles in life and death" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrm1666" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Mol Cell Biol" "fecha" => "2005" "volumen" => "6" "paginaInicial" => "505" "paginaFinal" => "510" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Anding AL, Baehrecke EH. Autophagy in Cell Life and Cell Death. In: Current topics in developmental biology 2015; 67-91." ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cell death by autophagy: facts and apparent artefacts" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/cdd.2011.146" "Revista" => array:6 [ "tituloSerie" => "Cell Death Differ" "fecha" => "2012" "volumen" => "19" "paginaInicial" => "87" "paginaFinal" => "95" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autophagy inhibition due to thymidine analogues as novel mechanism leading to hepatocyte dysfunction and lipid accumulation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/QAD.0b013e32835804f9" "Revista" => array:6 [ "tituloSerie" => "AIDS" "fecha" => "2012" "volumen" => "26" "paginaInicial" => "1995" "paginaFinal" => "2006" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI60580" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "2012" "volumen" => "122" "paginaInicial" => "2428" "paginaFinal" => "2438" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autophagy and mitophagy in the context of doxorubicin-induced cardiotoxicity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.18632/oncotarget.16944" "Revista" => array:6 [ "tituloSerie" => "Oncotarget" "fecha" => "2017" "volumen" => "8" "paginaInicial" => "46663" "paginaFinal" => "46680" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Studying Autophagy in Zebrafish" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Cells" "fecha" => "2017" "volumen" => "6" "paginaInicial" => "21" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Macrophage autophagy limits acute toxic liver injury in mice through down regulation of interleukin-1 β" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2015" "volumen" => "14" "paginaInicial" => "1" "paginaFinal" => "14" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autophagy protects from liver injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/cdd.2013.43" "Revista" => array:6 [ "tituloSerie" => "Cell Death Differ" "fecha" => "2013" "volumen" => "20" "paginaInicial" => "850" "paginaFinal" => "851" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Regulation of liver metabolism by autophagy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2015.09.042" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2015" "volumen" => "150" "paginaInicial" => "328" "paginaFinal" => "339" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhibition of hepatocyte autophagy increases tumor necrosis factor-dependent liver injury by promoting caspase-8 activation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/cdd.2013.21" "Revista" => array:6 [ "tituloSerie" => "Cell Death Differ" "fecha" => "2013" "volumen" => "20" "paginaInicial" => "878" "paginaFinal" => "887" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1083/jcb.200412022" "Revista" => array:6 [ "tituloSerie" => "J Cell Biol" "fecha" => "2005" "volumen" => "169" "paginaInicial" => "425" "paginaFinal" => "434" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The ontogeny of human drug-metabolizing enzymes: phase II conjugation enzymes and regulatory mechanisms" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Pharmacol Exp Ther" "fecha" => "2002" "volumen" => "300" "paginaInicial" => "361" "paginaFinal" => "366" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanisms of Drug Induced Liver Injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Liver Dis" "fecha" => "2008" "volumen" => "86" "paginaInicial" => "3279" "paginaFinal" => "3288" ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanisms in drug-induced liver injury: lessons" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/03602532.2011.602688" "Revista" => array:6 [ "tituloSerie" => "Drug Metab Rev" "fecha" => "2017" "volumen" => "44" "paginaInicial" => "88" "paginaFinal" => "106" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "UPR, autophagy and mitochondria crosstalk underlies the ER stress response" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Trends Biochem Sci" "fecha" => "2015" "volumen" => "13" "paginaInicial" => "36" "paginaFinal" => "37" ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Decoding cell death signals in liver inflammation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2013.03.033" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2013" "volumen" => "59" "paginaInicial" => "583" "paginaFinal" => "594" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autophagy is involved in en-doplasmic reticulum stress induced cell death of rat hepato-cytes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Surg Res 2013" "fecha" => "2014" "volumen" => "6" "paginaInicial" => "1" "paginaFinal" => "16" ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intracellular Signaling Mechanisms of Acetaminophen-Induced Liver Cell Death" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/toxsci/kfi336" "Revista" => array:6 [ "tituloSerie" => "Toxicol Sci" "fecha" => "2006" "volumen" => "89" "paginaInicial" => "31" "paginaFinal" => "41" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acetaminophen-induced acute liver failure: Results of a United States multicenter, prospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.20948" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2005" "volumen" => "42" "paginaInicial" => "1364" "paginaFinal" => "1372" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "45." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adi-ponectin protects against acetaminophen-induced mito-chondrial dysfunction and acute liver injury by promoting autophagy in mice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2014.05.033" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2014" "volumen" => "61" "paginaInicial" => "825" "paginaFinal" => "831" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "46." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Activation of autophagy protects against acetaminophen-in-duced hepatotoxicity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.24690" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2012" "volumen" => "55" "paginaInicial" => "222" "paginaFinal" => "232" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0235" "etiqueta" => "47." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNFα-mediated hepatotoxicity" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/toxsci/kfu072" "Revista" => array:6 [ "tituloSerie" => "Toxicol Sci" "fecha" => "2014" "volumen" => "140" "paginaInicial" => "144" "paginaFinal" => "159" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0240" "etiqueta" => "48." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cytochrome P450s: mechanisms and biological implications in drug metabolism and its interaction with oxidative stress" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Curr Drug Metab" "fecha" => "2014" "volumen" => "15" "paginaInicial" => "719" "paginaFinal" => "742" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0245" "etiqueta" => "49." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Microsomal oxidative damage promoted by acetaminophen metabolism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Toxicol Vitr" "fecha" => "2011" "volumen" => "25" "paginaInicial" => "1310" "paginaFinal" => "1313" ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0250" "etiqueta" => "50." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Suppression of autophagy dysregulates the antioxidant response and causes premature senescence of melanocytes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/jid.2014.439" "Revista" => array:6 [ "tituloSerie" => "J Invest Dermatol" "fecha" => "2015" "volumen" => "135" "paginaInicial" => "1348" "paginaFinal" => "1357" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0255" "etiqueta" => "51." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.plipres.2012.10.004" "Revista" => array:6 [ "tituloSerie" => "Prog Lipid Res" "fecha" => "2013" "volumen" => "52" "paginaInicial" => "165" "paginaFinal" => "174" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0260" "etiqueta" => "52." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacological Promotion of Autophagy Alleviates Steatosis and Injury in Alcoholic and Non-alcoholic Fatty Liver Conditions in Mice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2013.01.011" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2013" "volumen" => "58" "paginaInicial" => "993" "paginaFinal" => "999" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0265" "etiqueta" => "53." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Alerting E. Autophagy?: process and function. GENES Dev 2007; 2861-73." ] ] ] 53 => array:3 [ "identificador" => "bib0270" "etiqueta" => "54." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1083/jcb.200803137" "Revista" => array:6 [ "tituloSerie" => "J Cell Biol" "fecha" => "2008" "volumen" => "182" "paginaInicial" => "685" "paginaFinal" => "701" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0275" "etiqueta" => "55." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "3D tomography reveals connections between the phagophore and endoplasmic reticulum" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Autophagy" "fecha" => "2009" "volumen" => "5" "paginaInicial" => "1180" "paginaFinal" => "1185" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0280" "etiqueta" => "56." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ncb1991" "Revista" => array:6 [ "tituloSerie" => "Nat Cell Biol" "fecha" => "2009" "volumen" => "11" "paginaInicial" => "1433" "paginaFinal" => "1437" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0285" "etiqueta" => "57." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Autophagy" "fecha" => "2010" "volumen" => "6" "paginaInicial" => "764" "paginaFinal" => "776" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0290" "etiqueta" => "58." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "How to control self-digestion: transcriptional, post- transcriptional, and post-translational regulation of autophagy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Trends Cell Biol" "fecha" => "2014" "volumen" => "25" "paginaInicial" => "367" "paginaFinal" => "402" ] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0295" "etiqueta" => "59." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Regulation of autophagy: Modulation of the size and number of autophagosomes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "FEBS Lett" "fecha" => "2009" "volumen" => "42" "paginaInicial" => "115" "paginaFinal" => "125" ] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0300" "etiqueta" => "60." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autophagy signal transduction by ATG proteins: From hierarchies to networks" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00018-015-2034-8" "Revista" => array:6 [ "tituloSerie" => "Cell Mol Life Sci" "fecha" => "2015" "volumen" => "72" "paginaInicial" => "4721" "paginaFinal" => "4757" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 60 => array:3 [ "identificador" => "bib0305" "etiqueta" => "61." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of autophagy during the early neonatal starvation period" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature03029" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2004" "volumen" => "432" "paginaInicial" => "1032" "paginaFinal" => "1036" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 61 => array:3 [ "identificador" => "bib0310" "etiqueta" => "62." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Historical landmarks of autophagy research" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Nat Publ Gr" "fecha" => "2013" "volumen" => "24" "paginaInicial" => "9" "paginaFinal" => "23" ] ] ] ] ] ] 62 => array:3 [ "identificador" => "bib0315" "etiqueta" => "63." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Expression of the au-tophagy substrate SQSTM1/p62 is restored during prolonged starvation depending on transcriptional upregulation and autophagy-derived amino acids" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4161/auto.27344" "Revista" => array:6 [ "tituloSerie" => "Autophagy" "fecha" => "2014" "volumen" => "10" "paginaInicial" => "431" "paginaFinal" => "441" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 63 => array:3 [ "identificador" => "bib0320" "etiqueta" => "64." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhibition of soluble epoxide hydrolase modulates inflammation and autophagy in obese adipose tissue and liver: Role for omega-3 epoxides" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.1422590112" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci" "fecha" => "2015" "volumen" => "112" "paginaInicial" => "536" "paginaFinal" => "541" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 64 => array:3 [ "identificador" => "bib0325" "etiqueta" => "65." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nrf2 Promotes the Development of Fibrosis and Tumorigenesis in Mice with Defective Hepatic Autophagy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2014.04.043" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2015" "volumen" => "61" "paginaInicial" => "617" "paginaFinal" => "625" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 65 => array:3 [ "identificador" => "bib0330" "etiqueta" => "66." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transcriptional regulation of autophagy by an FXR/CREB axis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature13949" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2015" "volumen" => "516" "paginaInicial" => "108" "paginaFinal" => "111" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 66 => array:3 [ "identificador" => "bib0335" "etiqueta" => "67." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The noncoding RNA revolution-trashing old rules to forge new ones" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cell.2014.03.008" "Revista" => array:6 [ "tituloSerie" => "Cell" "fecha" => "2014" "volumen" => "157" "paginaInicial" => "77" "paginaFinal" => "94" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 67 => array:3 [ "identificador" => "bib0340" "etiqueta" => "68." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Massive rearrangements of cellular MicroRNA signatures are key drivers of hepatocyte dedifferentiation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.28780" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2016" "volumen" => "64" "paginaInicial" => "1743" "paginaFinal" => "1756" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 68 => array:3 [ "identificador" => "bib0345" "etiqueta" => "69." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long noncoding RNAs in kidney and cardiovascular diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrneph.2016.51" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Nephrol" "fecha" => "2016" "volumen" => "12" "paginaInicial" => "360" "paginaFinal" => "373" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 69 => array:3 [ "identificador" => "bib0350" "etiqueta" => "70." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature21034" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2016" "volumen" => "541" "paginaInicial" => "228" "paginaFinal" => "232" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 70 => array:3 [ "identificador" => "bib0355" "etiqueta" => "71." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The evolution of lncRNA repertoires and expression patterns in tetrapods" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature12943" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2014" "volumen" => "505" "paginaInicial" => "635" "paginaFinal" => "640" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 71 => array:3 [ "identificador" => "bib0360" "etiqueta" => "72." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "MicroRNAs in Drug-induced Liver Injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.14218/JCTH.2014.00015" "Revista" => array:6 [ "tituloSerie" => "J Clin Transl Hepatol" "fecha" => "2014" "volumen" => "2" "paginaInicial" => "162" "paginaFinal" => "169" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 72 => array:3 [ "identificador" => "bib0365" "etiqueta" => "73." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Structural bioinformatics A comprehensive benchmark of RNA - RNA interaction prediction tools for all domains of life" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/bioinformatics/btw728" "Revista" => array:6 [ "tituloSerie" => "Bioinformatics" "fecha" => "2017" "volumen" => "33" "paginaInicial" => "988" "paginaFinal" => "996" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 73 => array:3 [ "identificador" => "bib0370" "etiqueta" => "74." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The noncoding RNA revolution - Trashing old rules to forge new ones" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cell.2014.03.008" "Revista" => array:6 [ "tituloSerie" => "Cell" "fecha" => "2014" "volumen" => "157" "paginaInicial" => "77" "paginaFinal" => "94" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 74 => array:3 [ "identificador" => "bib0375" "etiqueta" => "75." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long Noncoding RNAs with Enhancer-like Function in Human Cells" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cell.2010.09.001" "Revista" => array:6 [ "tituloSerie" => "Cell" "fecha" => "2010" "volumen" => "143" "paginaInicial" => "46" "paginaFinal" => "58" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 75 => array:3 [ "identificador" => "bib0380" "etiqueta" => "76." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characterization of the structure, function, and mechanism of B2 RNA, an ncR-NA repressor of RNA polymerase II transcription" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1261/rna.310307" "Revista" => array:6 [ "tituloSerie" => "RNA" "fecha" => "2007" "volumen" => "13" "paginaInicial" => "583" "paginaFinal" => "596" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 76 => array:3 [ "identificador" => "bib0385" "etiqueta" => "77." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of onco-genic transcription factor B-MYB" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pgen.1003368" "Revista" => array:5 [ "tituloSerie" => "PLoS Genet" "fecha" => "2013" "volumen" => "9" "paginaInicial" => "e1003368" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 77 => array:3 [ "identificador" => "bib0390" "etiqueta" => "78." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The multilayered complexity of ceRNA crosstalk and competition" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature12986" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2014" "volumen" => "505" "paginaInicial" => "344" "paginaFinal" => "352" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 78 => array:3 [ "identificador" => "bib0395" "etiqueta" => "79." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ncomms7779" "Revista" => array:5 [ "tituloSerie" => "Nat Commun" "fecha" => "2015" "volumen" => "6" "paginaInicial" => "6779" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 79 => array:3 [ "identificador" => "bib0400" "etiqueta" => "80." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of a novel MTOR activator and discovery of a competing endogenous RNA regulating autophagy in vascular endothelial cells" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4161/auto.28363" "Revista" => array:6 [ "tituloSerie" => "Autophagy" "fecha" => "2014" "volumen" => "10" "paginaInicial" => "957" "paginaFinal" => "971" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 80 => array:3 [ "identificador" => "bib0405" "etiqueta" => "81." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Suppression of hepatocellular carcinoma by baculovirus-mediated expression of long non-coding RNA PTENP1 and MicroRNA regulation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.biomaterials.2014.12.023" "Revista" => array:6 [ "tituloSerie" => "Biomaterials" "fecha" => "2015" "volumen" => "44" "paginaInicial" => "71" "paginaFinal" => "81" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 81 => array:3 [ "identificador" => "bib0410" "etiqueta" => "82." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The long noncoding RNA HOTAIR activates autophagy by upregulating ATG3 and ATG7 in hepatocellular carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1039/c6mb00114a" "Revista" => array:6 [ "tituloSerie" => "Mol BioSyst" "fecha" => "2016" "volumen" => "12" "paginaInicial" => "2605" "paginaFinal" => "2612" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 82 => array:3 [ "identificador" => "bib0415" "etiqueta" => "83." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "lncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Nat Cell Biol" "fecha" => "2015" "volumen" => "10" "paginaInicial" => "552" "paginaFinal" => "554" ] ] ] ] ] ] 83 => array:3 [ "identificador" => "bib0420" "etiqueta" => "84." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Down regulated lncRNA MEG3 eliminates mycobacteria in macrophages via autophagy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/srep19416" "Revista" => array:5 [ "tituloSerie" => "Sci Rep" "fecha" => "2016" "volumen" => "6" "paginaInicial" => "19416" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 84 => array:3 [ "identificador" => "bib0425" "etiqueta" => "85." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A new microRNA signal pathway regulated by long noncoding RNA TGFB2-OT1 in autophagy and inflammation of vascular endothelial cells" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/15548627.2015.1106663" "Revista" => array:6 [ "tituloSerie" => "Autophagy" "fecha" => "2015" "volumen" => "11" "paginaInicial" => "2172" "paginaFinal" => "2183" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 85 => array:3 [ "identificador" => "bib0430" "etiqueta" => "86." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Down-regulation of Risa improves insulin sensitivity by enhancing autophagy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1096/fj.201500058R" "Revista" => array:6 [ "tituloSerie" => "FASEB J" "fecha" => "2016" "volumen" => "30" "paginaInicial" => "3133" "paginaFinal" => "3145" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 86 => array:3 [ "identificador" => "bib0435" "etiqueta" => "87." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PCGEM1 stimulates proliferation of osteoarthritic synoviocytes by acting as a sponge for miR-770" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jor.23046" "Revista" => array:6 [ "tituloSerie" => "J Orthop Res" "fecha" => "2016" "volumen" => "34" "paginaInicial" => "412" "paginaFinal" => "418" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 87 => array:3 [ "identificador" => "bib0440" "etiqueta" => "88." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Down-Regulation of Lncrna MALAT1 Attenuates Neuronal Cell Death Through Suppressing Beclin1-Dependent Autophagy by Regulating Mir-30a in Cerebral Ischemic Stroke" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000480337" "Revista" => array:6 [ "tituloSerie" => "Cell Physiol Biochem" "fecha" => "2017" "volumen" => "43" "paginaInicial" => "182" "paginaFinal" => "194" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 88 => array:3 [ "identificador" => "bib0445" "etiqueta" => "89." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbrc.2017.08.070" "Revista" => array:6 [ "tituloSerie" => "Biochem Biophys Res Commun" "fecha" => "2017" "volumen" => "492" "paginaInicial" => "480" "paginaFinal" => "486" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 89 => array:3 [ "identificador" => "bib0450" "etiqueta" => "90." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The HIF-2α-MALAT1-miR-216b axis regulates multi-drug resistance of hepatocellular carcinoma cells via modulating autophagy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbrc.2016.08.065" "Revista" => array:6 [ "tituloSerie" => "Biochem Biophys Res Commun" "fecha" => "2016" "volumen" => "478" "paginaInicial" => "1067" "paginaFinal" => "1073" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 90 => array:3 [ "identificador" => "bib0455" "etiqueta" => "91." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Huang J, Yang Y, Fang F, Liu K. MALAT1 modulates the autophagy of retinoblastoma cell through miR-124-mediated stx17 regulation. J Cell Biochem Published Online First: 19 January 2018." ] ] ] 91 => array:3 [ "identificador" => "bib0460" "etiqueta" => "92." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long noncoding RNA MALAT1 regulates autophagy associated chemoresistance via miR-23b-3p sequestration in gastric cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12943-017-0743-3" "Revista" => array:5 [ "tituloSerie" => "Mol Cancer" "fecha" => "2017" "volumen" => "16" "paginaInicial" => "174" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 92 => array:3 [ "identificador" => "bib0465" "etiqueta" => "93." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ncomms7779" "Revista" => array:5 [ "tituloSerie" => "Nat Commun" "fecha" => "2015" "volumen" => "6" "paginaInicial" => "6779" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 93 => array:3 [ "identificador" => "bib0470" "etiqueta" => "94." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "LncRNA HULC triggers autophagy via stabilizing Sirt1 and attenuates the chemosensitivity of HCC cells" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/onc.2016.521" "Revista" => array:6 [ "tituloSerie" => "Oncogene" "fecha" => "2017" "volumen" => "36" "paginaInicial" => "3528" "paginaFinal" => "3540" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 94 => array:3 [ "identificador" => "bib0475" "etiqueta" => "95." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long non-coding RNA AC023115.3 suppresses chemoresistance of glioblastoma by reducing autophagy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ …7] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Biochim Biophys Acta" "fecha" => "2017" "volumen" => "1864" "paginaInicial" => "1393" "paginaFinal" => "1404" ] ] ] ] ] ] 95 => array:3 [ "identificador" => "bib0480" "etiqueta" => "96." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long non-coding RNA HNF1A-AS1 functioned as an oncogene and autophagy promoter in hepatocellular carcinoma through sponging hsa-miR-30b-5p" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbrc.2016.04.054" "Revista" => array:6 [ "tituloSerie" => "Biochem Biophys Res Commun" "fecha" => "2016" "volumen" => "473" "paginaInicial" => "1268" "paginaFinal" => "1275" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 96 => array:3 [ "identificador" => "bib0485" "etiqueta" => "97." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PVT1 affects growth of glioma microvascular endothelial cells by negatively regulating miR-186" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Tumor Biol" "fecha" => "2017" "volumen" => "39" ] ] ] ] ] ] 97 => array:3 [ "identificador" => "bib0490" "etiqueta" => "98." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Knockdown of long non-coding RNA HOTAIR increases miR-454-3p by targeting Stat3 and Atg12 to inhibit chondrosarcoma growth" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/cddis.2017.31" "Revista" => array:5 [ "tituloSerie" => "Cell Death Dis" "fecha" => "2017" "volumen" => "8" "paginaInicial" => "e2605" "link" => array:1 [ …1] ] ] ] ] ] ] 98 => array:3 [ "identificador" => "bib0495" "etiqueta" => "99." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A long non-coding RNA, GAS5, plays a critical role in the regulation of miR-21 during osteoarthritis" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jor.22718" "Revista" => array:6 [ "tituloSerie" => "J Orthop Res" "fecha" => "2014" "volumen" => "32" "paginaInicial" => "1628" "paginaFinal" => "1635" "link" => array:1 [ …1] ] ] ] ] ] ] 99 => array:3 [ "identificador" => "bib0500" "etiqueta" => "100." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PCGEM1 stimulates proliferation of osteoarthritic synoviocytes by acting as a sponge for miR-770" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jor.23046" "Revista" => array:6 [ "tituloSerie" => "J Orthop Res" "fecha" => "2016" "volumen" => "34" "paginaInicial" => "412" "paginaFinal" => "418" "link" => array:1 [ …1] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/0000001700000003/v1_201905160920/S1665268119301929/v1_201905160920/en/main.assets" "Apartado" => array:4 [ "identificador" => "77721" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/16652681/0000001700000003/v1_201905160920/S1665268119301929/v1_201905160920/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119301929?idApp=UINPBA00004N"]

Statistics

Juan Zhou*,**, Yi Li*, XinYu Liu*, Yunzhu Long**, Jun Chen

Corresponding author

chenjun66@csu.edu.cn

Corresponding author.

* Liver Diseases Center, Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China

** Department of Infectious Diseases, The affiliated Zhuzhou Hospital Xiangya Medical college, Central South University, Zhuzhou, Hunan, P.R. China

Read

1957

Times
was read the article

464

Total PDF

1493

Total HTML

Share statistics

 array:24 [
  "pii" => "S1665268119301929"
  "issn" => "16652681"
  "doi" => "10.5604/01.3001.0011.7381"
  "estado" => "S300"
  "fechaPublicacion" => "2018-05-01"
  "aid" => "70049"
  "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
  "copyrightAnyo" => "2018"
  "documento" => "article"
  "crossmark" => 0
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "fla"
  "cita" => "Ann Hepatol. 2018;17:355-63"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 150
    "formatos" => array:3 [
      "EPUB" => 16
      "HTML" => 96
      "PDF" => 38
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S1665268119301930"
    "issn" => "16652681"
    "doi" => "10.5604/01.3001.0011.7382"
    "estado" => "S300"
    "fechaPublicacion" => "2018-05-01"
    "aid" => "70050"
    "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Ann Hepatol. 2018;17:364-91"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 196
      "formatos" => array:3 [
        "EPUB" => 10
        "HTML" => 114
        "PDF" => 72
      ]
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "titulo" => "Association Between Hepatitis C Virus and Chronic Kidney Disease&#58; A Systematic Review and Meta-Analysis"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "364"
          "paginaFinal" => "391"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "f0015"
          "etiqueta" => "Figure 3"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr3.jpeg"
              "Alto" => 344
              "Ancho" => 509
              "Tamanyo" => 15228
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">aHR and 95&#37; confidence intervals for each study &#40;n &#61; 15 longitudinal studies&#59; n &#61; 2&#44;299&#44;134 unique patients&#41; &#40;Outcome&#58; incidence of CKD&#41;&#46; aHR of CKD associated with HCV &#40;longitudinal surveys&#41;&#44; 1&#46;54 &#40;95&#37; CI&#44; 1&#44;26&#59; 1&#46;87&#41; &#40;P &#60; 0&#46;001&#41;&#46; Q value by &#967;<span class="elsevierStyleSup">2</span> test&#44; 500&#46;3 &#40;P &#61; 0&#46;0001&#41;&#44; I<span class="elsevierStyleSup">2</span> &#61; 97&#46;2&#37;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Fabrizio Fabrizi, Francesca M&#46; Donato, Piergiorgio Messa"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Fabrizio"
              "apellidos" => "Fabrizi"
            ]
            1 => array:2 [
              "nombre" => "Francesca M&#46;"
              "apellidos" => "Donato"
            ]
            2 => array:2 [
              "nombre" => "Piergiorgio"
              "apellidos" => "Messa"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119301930?idApp=UINPBA00004N"
    "url" => "/16652681/0000001700000003/v1_201905160920/S1665268119301930/v1_201905160920/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S1665268119301917"
    "issn" => "16652681"
    "doi" => "10.5604/01.3001.0011.7380"
    "estado" => "S300"
    "fechaPublicacion" => "2018-05-01"
    "aid" => "70048"
    "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Ann Hepatol. 2018;17:345-54"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 401
      "formatos" => array:3 [
        "EPUB" => 17
        "HTML" => 278
        "PDF" => 106
      ]
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "titulo" => "Non-Alcoholic Fatty Liver Disease in Children and Adolescents&#58; Lifestyle Change - a Systematic Review and Meta-Analysis"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "345"
          "paginaFinal" => "354"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "f0015"
          "etiqueta" => "Figure 3&#46;"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr3.jpeg"
              "Alto" => 434
              "Ancho" => 669
              "Tamanyo" => 70539
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Combined effect of the intervention on ALT levels&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Melina Utz-Melere, Cristina Targa-Ferreira, Bernardo Lessa-Horta, Matias Epifanio, Marialena Mouzaki, Angelo A&#46; Mattos"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Melina"
              "apellidos" => "Utz-Melere"
            ]
            1 => array:2 [
              "nombre" => "Cristina"
              "apellidos" => "Targa-Ferreira"
            ]
            2 => array:2 [
              "nombre" => "Bernardo"
              "apellidos" => "Lessa-Horta"
            ]
            3 => array:2 [
              "nombre" => "Matias"
              "apellidos" => "Epifanio"
            ]
            4 => array:2 [
              "nombre" => "Marialena"
              "apellidos" => "Mouzaki"
            ]
            5 => array:2 [
              "nombre" => "Angelo A&#46;"
              "apellidos" => "Mattos"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119301917?idApp=UINPBA00004N"
    "url" => "/16652681/0000001700000003/v1_201905160920/S1665268119301917/v1_201905160920/en/main.assets"
  ]
  "en" => array:17 [
    "idiomaDefecto" => true
    "titulo" => "LncRNA-Regulated Autophagy and its Potential Role in Drug-induced Liver Injury"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "355"
        "paginaFinal" => "363"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Juan Zhou, Yi Li, XinYu Liu, Yunzhu Long, Jun Chen"
        "autores" => array:5 [
          0 => array:3 [
            "nombre" => "Juan"
            "apellidos" => "Zhou"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;&#42;</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Yi"
            "apellidos" => "Li"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "XinYu"
            "apellidos" => "Liu"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Yunzhu"
            "apellidos" => "Long"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;&#42;</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          4 => array:4 [
            "nombre" => "Jun"
            "apellidos" => "Chen"
            "email" => array:1 [
              0 => "chenjun66@csu.edu.cn"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:2 [
          0 => array:3 [
            "entidad" => "Liver Diseases Center&#44; Department of Infectious Diseases&#44; The Second Xiangya Hospital&#44; Central South University&#44; Changsha&#44; Hunan 410011&#44; China"
            "etiqueta" => "&#42;"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Department of Infectious Diseases&#44; The affiliated Zhuzhou Hospital Xiangya Medical college&#44; Central South University&#44; Zhuzhou&#44; Hunan&#44; P&#46;R&#46; China"
            "etiqueta" => "&#42;&#42;"
            "identificador" => "aff0010"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#42;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "f0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 426
            "Ancho" => 696
            "Tamanyo" => 64126
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">ATGs involved in the initiation of autophagy induced by endoplasmic reticulum &#40;ER&#41; stress&#46; First&#44; the ULK1-ATG13-FIP200-ATG101 complex is activated&#46; Then&#44; PtdIns3K class III complexes &#40;Beclin1-VPS15-VPS34&#41; are induced to transform phosphatidylinositol 3-phosphate &#40;PtdIns3P&#41; intensified by ATG14&#44; followed by recruitment of downstream effectors such as DFCP1 and WIPI-family&#46; ATG12-ATG5-ATG16L1 complex exerts its E3-like function and thus catalyzes LC3-I&#44; leading to LC3 cleavage by ATG4 to LC3-II&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Drug-induced liver injury &#40;DILI&#41; has gained significant attention worldwide in the last decades on account of its significant morbidity and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#8211;</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> It is one of the most common causes of acute liver failure to date in the United States and Europe&#44; and a leading reason for emergent liver transplant&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Further understanding of the pathogenesis of DILI might have important value for preventing and treating the disease&#46; The pathogenesis of drug-induced hepatitis is considerably complex&#44; involving multiple pathological processes&#44; such as liver cell damage&#44; intracellular fat change&#44; fibrosis&#44; apoptosis&#44; necrosis&#44; and so on&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Although the pattern of DILI can be generalized as intrinsic types referring to drugs with dose-dependent and idiosyncratic types characterizing by an adaptive immune attack&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> the common downstream events were the imbalance between pathways to injury and restorative tissue repair&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> It is related to not only the type and nature of the drug&#44; but also the genetic background of the individual&#46; However&#44; the ultimate common pathway is the activation of the cell death signal&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Results from a genomics approach revealed that endoplasmic reticulum &#40;ER&#41; stress and nuclear factor-erythroid 2-related factor 2 &#40;Nrf2&#41;signaling are two major pathways involved in DILI&#46; Other is subsequent protein kinase R-like ER kinase &#40;PERK&#41;&#44; activating transcription factor 4 &#40;ATF4&#41;&#44; and C&#47;EBP homologous protein &#40;CHOP&#41; activation&#44; which may be the crosstalk with pro-apoptosis signaling&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> It is supported by the research on CHOP knockout &#40;KO&#41; mice that can protect liver cells from APAP-induced damage and reduce necrosis&#44; exhibiting proliferation and increased hepatocyte survival&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Therefore&#44; ER stress&#44; which has dual effects either cause apoptosis or protective effect&#44; is the key process in the pathogenesis of DILI&#46; In neurons&#44; ATF5 upregulation induced mainly by ER stress does not lead to apoptosis&#44; implicating that ER stress acts as a prosurvival mechanism&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Moreover&#44; inhibition of IRE1a followed by ER stress enhances the cytotoxic effects&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The role of ER stress in promoting cell survival and death is still unknown&#46; Therefore&#44; this review focused on the molecular mechanism of autophagy referring to restorative tissue repair regulated by long noncoding RNA &#40;lncRNA&#41; for a better understanding of the pathogenesis&#44; diagnosis&#44; and treatment of DILI&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Autophagy and Dili</span><p id="p0010" class="elsevierStylePara elsevierViewall">Autophagy is a process designed to sequester and degrade intracellular components&#44; beginning with the formation of double-membrane vesicles tightly controlled by the autophagy-related genes &#40;ATG&#41;&#46; It is a critical adaptive response for cell survival&#44; which can be dramatically induced by starvation and a broad range of stressors&#44; such as ER stress&#44; pathogen infection&#44; oxidative stress&#44; and so on&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> The failure to get rid of intracellular wastes by autophagy greatly disrupts homeostasis&#44; which can invariably induce cell death and inflammation consequently resulting in tissue injury&#46; Autophagy acts as an intracellular degradation process associated with lysosomes&#46; It mainly targets cy-tosolic components such as abnormal proteins and or-ganelles&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> It is essentially a self-repairing process to deal with potential risk factors for intracellular physiological processes and prolong the life of cells via energy regeneration<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> and removal of harmful or useless substances&#46; Otherwise&#44; apoptosis can sequentially be elicited as another protective factor to relieve stress when autophagy fails to perform its functions&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> So far&#44; more than 40 autophagy-related genes have been identified in yeast and mammals&#44; which tightly control the intracellular adaptive process via multiple signaling pathways&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> A total of 15 core <span class="elsevierStyleItalic">ATG</span> genes &#40;<span class="elsevierStyleItalic">ATG</span>1-10&#44; 12-14&#44; 16&#44; and 18&#41;&#44; which are highly conserved in mammals&#44; are required for selective autophagy for protein aggregates&#44; damaged mitochondria&#44; excessive peroxisomes&#44; ribosomes&#44; and invading pathogens&#46; The expression and regulation of these genes are closely related to the death pathway&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">The hepatocytes have a higher capacity for autophagy compared with other cell types because of a large number of ER&#44; mitochondria&#44; and lysosomal enzymes required for multiple metabolic functions and to cope with different biological or chemical stimuli&#44; ultimately ensuring cellular homeostasis&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> The ER is one of the main sites for drug metabolism in the liver&#44; and also the assembly and modification of secretory and integral membrane proteins&#46; ER stress is the stimulus for autophagy&#46; Further&#44; ER is the initiation site for the biogenesis of autophago-somes&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> ER stress and autophagy are related to apoptosis and hence have been recognized as critical pathways in the regulation of cell death&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Recent studies have demonstrated essential protective functions of autophagy in hepatocytes during liver injury&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26</span></a><span class="elsevierStyleSup">&#8211;</span><a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> Thymidine analogs were found to inhibit autophagy on constitutive and induced levels in hepatocytes&#44; increasing reactive oxygen species production&#44; lipid accumulation&#44; and hepatic dysfunction&#44; and thereby resulting in apoptosis&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Doxorubicin&#44; an antibiotic drug used for chemotherapy in various cancers&#44; induces cardiotoxicity&#44; which is consistent with dysregulated autophagy and autophagosome formation shown by a variety of approaches in cardiomyocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Knockout of <span class="elsevierStyleItalic">ATG5</span> the autophagy gene has confirmed that deficiency of autophagy can increase acute liver injury induced by D-galactosamine&#47;lipopolysaccharides in mice&#46; Similar results were observed with a knockout of the gene <span class="elsevierStyleItalic">Atg</span>7&#44; leading to liver injury with a hepatocyte-specific loss of autophagy&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> Deletion of the autophagy gene <span class="elsevierStyleItalic">Atg</span>7 led to the accumulation of concentric membranous structures&#44; which were continuous with the rough ER&#46; These structures were surrounded by various aberrant mitochondria and lipid droplets&#46; Disorganized hepatic lobules and cell swelling were noted on histological analysis&#44; while no hepatocyte proliferation or regeneration was observed&#46; These findings were consistent with the protective role of autophagy in eliminating abnormal organelles for maintaining normal liver metabolism&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> ER is an original site for autophagy&#46; Moreover&#44; autophagy closely related to ER is essential in protecting the hepatocytes from damage in metabolic processes&#46;</p><p id="p0020" class="elsevierStylePara elsevierViewall">Drug metabolism in hepatocytes primarily occurs on ER&#46; Hence&#44; accumulation of reactive metabolites and conjugate proteins can strikingly increase the ER stress in response to overdose or long-term use of drugs&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37</span></a><span class="elsevierStyleSup">&#8211;</span><a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> ER stress is resolved by the activation of the unfolded protein response&#44; which can be elicited by three stress sensors inositol-requiring protein 1&#945;&#44; activating transcription factor 6&#44; and protein kinase RNA-like ER kinase to orchestrate the normal ER function&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> The collaboration of these processes helps in deciding the scale of adaptive capacity and thus governs whether cells will re-establish homeostasis or activate cell death programs via an internal pathway of apoptosis with inhibition of autophagy&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> Existing data implicated that autophagy&#44; as a downstream mediator of ER stress&#44; had a pronounced decrease in cell viability during drug-induced damage of rat hepatocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> The mechanism underlying hepatotoxicity caused by drugs has not been recognized yet&#46; However&#44; it seems that these mechanisms are closely related to the increase in damaged organelles and nonfunctional proteins during biotransformation to metabolites&#44; resulting in increasing ER stress and oxidative stress&#46; For instance&#44; acetaminophen &#40;APAP&#41;&#44; which is widely used as an antipyretic and analgesic drug&#44; is the most common source of severe hepatotoxicity&#46; APAP-induced hepatotoxicity has been demonstrated to be mediated mainly via its reactive metabolite&#46; During APAP overdose&#44; <span class="elsevierStyleItalic">N</span>-acetyl-<span class="elsevierStyleItalic">p</span>-benzo-quinone imine &#40;NAPQI&#41;&#44; which is generated from APAP metabolism by cytochrome P450&#44; can deplete hepatic stores of glutathione&#44; interfering with cellular redox homeostasis&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> The remaining NAPQI reacts with many cellular proteins and induces autophagy acting as an adaptive response to remove damaged organelles&#44; especially mitochondria&#46; Furthermore&#44; induction of autophagy inhibited APAP-induced hepatotoxicity&#44; preventing against liver injury&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> In addition to ER stress&#44; NRF2-mediated oxidative stress response has implicated in DILI&#44; which suggested excessive reactive oxygen species &#40;ROS&#41; were generated by the oxidative metabolism of drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> It is generally believed that ROS result from both the NAD&#40;P&#41;H oxidase &#40;NOX&#41; and CYP450 system using co-factor NADPH&#44; which is following by the oxidative damage mainly manifested as lipid peroxidation&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> However&#44; ROS generation can be largely attributed to a NOX activity rather than the CYP450 system when incubated acetaminophen and NADPH in microsomes of rat liver&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> The recent development indicated that autophagy-deficient caused oxidative stress increasing in melanocytes&#44; also the upregulation of ROS&#44; Nrf2 antioxidant signaling and lipid oxidation&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> Whether these phenomena existing in hepato-cytes need further experiments to prove&#46; Although the hepatocyte damage induced by different drugs may have varied pathways&#44; the central factors are the reactive metabolites&#44; resulting in abnormal proteins or organelles interfering with the normal physiological program&#46; This provides the framework for thinking about ER stress-induced autophagy&#44; which is a cellular adaptive response to cope with these stresses involved in liver injury caused by drugs&#46; Researchers suggested ER stress and au-tophagy can constitute an effective defense mechanism against multiple insult from lipid metabolism&#44; alcohol and non-alcoholic fatty liver in hepatocytes which may be similar to DILI&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> It has been proven autophagy-enhancing drugs can alleviate liver steatosis&#44; liver injury&#44; and dyslip-idemia in both alcohol-fed and HFD&#40;high fat diet&#41;-fed mice&#44;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a> yet it is not clear how autophagy is initiated in these contexts that may be different from DILI&#46; Further studies to clarify the intensity of autophagy induced by ER stress&#44; particularly originating from drug biotransformation in hepatocytes&#44; might provide important information on DILI&#46;</p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Regulation of Autophagy</span><p id="p0025" class="elsevierStylePara elsevierViewall">The performance of autophagy includes two steps&#58; formation of autophagosomes and generation of autolyso-somes from the fusion of double-membrane vesicles with lysosomes&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> The autophagosomal membrane originates from the ER&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> as confirmed by two groups that demon-strated the physical connection between the ER and isolation membrane using 3D electron microscopy&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a></p><p id="p0030" class="elsevierStylePara elsevierViewall">So far&#44; three critical protein complexes have been identified&#44; including the ULK1-ATG13-FIP200-ATG101 complex&#44; the Beclin1-ATG14-Vps34-Vps15 &#40;class III PI3-kinase&#41; complex&#44; and the ATG12-ATG5-ATG16L1 complex&#46; The ULK1 complex appears to be the most upstream unit&#44; followed by ATG14-containing PI3-kinase complex&#44; which together regulate the formation of both DFCP1 and WIPI-1 structures&#46; Most downstream events are activation of the ATG12 system and the LC3<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> &#40;<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>&#41;&#46; These proteins participate in different steps of autophagy in a temporal order based on their roles in autophagosome formation and are regulated by each other through diverse pathways relying on different intracellular stimuli or different cell types&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> Therefore&#44; regulation of autophagy involves not only the interaction between the core ATG proteins but also variation in ATG genes at the transcrip-tional and posttranslational levels&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> Autophagy occurs at a constitutive basal level but can be upregulated by different types of stresses such as starvation&#44; damaged intracellular components&#44; or pathogen infection&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a> It first involves the recruitment and co-working of core ATG proteins&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> followed by changes at the transcriptional and post-tran-scriptional levels&#44;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> which probably govern the extent of autophagy to cope with a strong or prolonged stimulus&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0035" class="elsevierStylePara elsevierViewall">Recent progresses in autophagy research in genetically modified mice &#40;especially the study on <span class="elsevierStyleItalic">Atg5</span> KO mice&#41; have revealed the important role of some ATG genes&#44; indicating the importance of autophagy for survival&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a> Other four phenotypes of Atg7&#44; Atg9&#44; and Atg16L1 have shown a result similar to that in Atg5 using the gene KO mice model&#46; Atg5&#44; Atg7&#44; Atg9&#44; Atg16L1&#44; Beclin 1&#44; and FIP200 are indispensable components for the formation of autophagosomes&#44;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> implying the involvement of these proteins in the regulation of autophagy&#46; In line with these findings&#44; the expression of ATG3&#44; ATG5&#44; ATG12&#44; ULK1&#44; LC3B&#44; Beclin-1&#44; and GABA&#40;A&#41;receptor-associated protein like 1 was downregulated in human osteoarthritis cartilage compared with the normal cartilage&#44; whereas the expression of mTOR was significantly upregulated&#46; The expression levels of these proteins could be subsequently restored on deleting mTOR gene in the cartilage of mice&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a> The involvement of ATG5&#44; ATG7&#44; ATG9&#44; and ATG16L in the conjugation system&#44; which directly participates in the formation of phosphatidylethanolamine with the expansion of autophagosomes &#40;<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> suggests that the intermediate stage presumably is vital in regulating the extent of autophagy&#46; For instance&#44; an inhibitor of soluble epoxide hydrolase can recover the levels of Atg12-Atg5 and LC3-II conjugates&#44; resulting in the upregulation of hepatic autophagy to modulate inflammation in fat-1 mice&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">64</span></a> Also&#44; deletion of Atg5 in hepatocytes can lead to loss of au tophagy&#44; consequently increasing apoptosis&#44; inflammation&#44; and fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">65</span></a> During prolonged starvation&#44; the expression level of SQSTM1&#47;p62&#44; a substrate protein degraded by autophagy&#44; is determined by three factors&#58; reduction in au-tophagic degradation&#44; activation of transcriptional factors&#44; and availability of amino acids needed to synthesize new proteins&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a></p><elsevierMultimedia ident="f0010"></elsevierMultimedia><p id="p0040" class="elsevierStylePara elsevierViewall">Other substrates involved in autophagy might have similar regulatory processes&#46; A study on the transcriptional regulation of autophagy revealed that the fed-state sensing nuclear receptor inhibited autophagy by binding to 178 &#40;of 230&#41; autophagy-related genes for decreasing their expression&#44; and CREB &#40;the fasting transcriptional activator&#41; promoted autophagic degradation of lipids via upregulating 112 genes under nutrient-deprived conditions in mouse liver&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">66</span></a></p><p id="p0045" class="elsevierStylePara elsevierViewall">These signaling pathways and transcriptional or post-transcriptional factors manipulate autophagy and serve as critical components to dispose of stress or changes in the liver&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="p0050" class="elsevierStylePara elsevierViewall">Ample evidence indicates different classes of RNA&#44; ranging from small to long noncoding RNAs&#44; as key regulators of gene expression&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">67</span></a> In a hepatocyte dedifferentiation study&#44; massive alterations of noncoding transcriptome were found&#44; hallmarked by increased expression of small nucleolar RNAs&#44; lncRNAs&#44; microRNAs &#40;miRNAs&#41;&#44; and ribosomal genes&#44; preceding changes in protein-coding genes&#46; Notably&#44; only the regulation of lncRNAs among the ncRNAs displayed significant temporal and directional congruity with the profiles of coding genes&#46; This showed that lncRNA primarily took part in regulating the expression of coding genes&#44; influencing protein output&#46; On the contrary&#44; lncRNA might be generated from the transcription of protein-coding genes&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">68</span></a> Above all&#44; it is reasonable to speculate that the regulation of the transcription of ATG was partially manipulated by lncRNA&#46; Therefore&#44; an in-depth understanding of the molecular mechanisms underlying the manipulation of autophagy is crucial to obtain new insights on the strategies of diagnosing and treating autophagy-associated liver diseases&#46;</p><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">IncRNA-regulated autophagy</span><p id="p0055" class="elsevierStylePara elsevierViewall">LncRNA &#40;length &#62; 200 bases&#41; have attracted the attention of many researchers recently because of their involvement in diverse fundamental processes&#44; in particular gene expression&#44; which refers to recruiting chromatin-modify-ing complexes&#44; enhancing transcription&#44; decoying miR-NAs&#44; providing a scaffold&#44; and encoding peptides&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">69</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">70</span></a></p><p id="p0060" class="elsevierStylePara elsevierViewall">A study on the evolutionary history of lncRNA revealed that lncRNA promoters were more frequently associated with transcription factors compared with random intergenic regions&#44; suggesting their potential role in tran-scription&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">71</span></a> MiRNA has always been considered as the central player in controlling gene expression at the post-transcriptional level&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">72</span></a> It has been extensively studied as a repressor of gene expression or cleavage of mRNA&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">73</span></a> During the last decade&#44; increasing evidence has indicated that lncRNA with low or no protein-coding potential may be equally important in the regulation of gene expression&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">74</span></a> A large number of studies have confirmed the role of lncRNA in diverse biological functions via different mechanisms&#44; including regulating the expression of adjoining protein&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">75</span></a> negatively regulating RNA polymerase II &#40;RNAP II&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">76</span></a> and regulating alternative splicing<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">77</span></a> and microRNA sponges termed as competing endogenous RNAs &#40;ceRNAs&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">78</span></a> The most important function of RNA is to synthesize the proteins necessary for life activities&#46; The interaction between different kinds of RNA&#44; in particular ncRNA and mRNA&#44; has a decisive role in regulating transcription and translation&#46; After all&#44; communication between the same kind of RNAs takes precedence over heterogeneous crosstalk&#46; The challenge was that these experiments revealed what happened&#44; but not the coordination in time and space&#46; The present study paid close attention to some of the recent data concerning the involvement of lncRNA in regulating different steps of autophagy especially the expression of related proteins&#44; giving a better understanding of the process&#46;</p><p id="p0065" class="elsevierStylePara elsevierViewall">Some studies found that lncRNA APF &#40;AK079427&#44; 1695 nt long&#41; regulates the occurrence of autophagy via inhibiting miR-188-3p in a sequence-specific manner to significantly protect the expression of ATG7 in the myocardial cells of mice&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">79</span></a> In addition&#44; the overexpression of lncRNA &#40;FLJ11812&#44; located in the 3&#39; UTR of TGFB2 gene&#44; contains 1370 nt&#41; could promote autophagy by increasing the ATG13 protein level&#46; Furthermore&#44; FLJ11812 competes to bind with MIR4459&#44; which targets ATG13 to down regulate its expression&#44; which is analogous to the mechanism of APF acting as a competing endogenous RNA &#40;ceRNA&#41; to control ATG13 level<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a>&#46; LncRNA PTENP1 indirectly contributes to autophagy by effectively upregulating ULK1&#44; ATG7&#44; and p62 levels via the antagonizing action of miR-17 in HCC cells&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a> Another study confirmed that the overexpression of HOTAIR&#44; an lncRNA that could promote the activation of autophagy in HCC cell lines&#44; was equivalent to upregulating the expression levels of ATG3 and ATG7 &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">82</span></a> These findings further explained the importance of the expression of the aforementioned key genes in modulating autophagy&#46; Also&#44; lncRNA had a strong influence on the protein expression&#46; LncRNA has been proved to be crucial in regulating autophagy and participate in the pathophysiological processes of various human diseases&#44; such as NBR2 and tumor development&#44;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">83</span></a> MEG3 and bacterial infections&#44;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">84</span></a> TGFB2-OT1 and in-flammation&#44;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">85</span></a> Risa and insulin sensitivity&#44;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">86</span></a> PCGEM1 and osteoarthritic synoviocytes&#44;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">87</span></a> and so on&#46; The regulation network of gene expression involves lncRNA in au-tophagy&#44; providing a new insight into the mechanism of hepatocyte injury&#46; The liver is found to be rich in lncR-NA&#44; followed by testes and neural tissues in the body&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">71</span></a> Therefore&#44; further understanding of the role of lncRNA during pathophysiological conditions can help in developing potential diagnostic and therapeutic methods for patients with DILI&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia></span></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Conclusions</span><p id="p0070" class="elsevierStylePara elsevierViewall">Autophagy is the most basic protective pattern for normal physical activities and survival&#46; Exploring the regulatory mechanism influencing the extent of autophagy at the molecular level&#44; especially for protein transcription and translation&#44; can substantially contribute to understanding the pathophysiology of cellular damage&#46; While manipulating autophagy&#44; networks between lncRNA and mRNA might be crucial for key gene expression&#44; which might help to understand the basic pathophysiological conditions and the development of autophagy-associated DILI&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:7 [
        0 => array:3 [
          "identificador" => "xres1190755"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abs0010"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1110032"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "s0005"
          "titulo" => "Introduction"
        ]
        3 => array:2 [
          "identificador" => "s0010"
          "titulo" => "Autophagy and Dili"
        ]
        4 => array:3 [
          "identificador" => "s0015"
          "titulo" => "Regulation of Autophagy"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "s0020"
              "titulo" => "IncRNA-regulated autophagy"
            ]
          ]
        ]
        5 => array:2 [
          "identificador" => "s0025"
          "titulo" => "Conclusions"
        ]
        6 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-02-11"
    "fechaAceptado" => "2018-03-07"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1110032"
          "palabras" => array:4 [
            0 => "Autophagy"
            1 => "Autophagy-related genes"
            2 => "Drug-induced liver injury"
            3 => "Long noncoding RNA"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><p id="sp0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Introduction and aim&#46;</span> Autophagy and its regulated pathways participate in many important cellular physiology and pathological processes involving protein aggregates&#44; damaged mitochondria&#44; excessive peroxisomes&#44; ribosomes&#44; and invading pathogens&#46; This study aimed to review recently published studies and further describe the long noncoding RNA &#40;lncRNA&#41;-regulated autophagy during drug-induced liver injury &#40;DILI&#41;&#46;</p><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Material and methods</span>&#46; DILI&#44; autophagy&#44; autophagy-related genes &#40;ATGs&#41;&#44; and lncRNA were used as key words to search published studies from PubMed&#44; Google Scholar&#44; and Web of Science&#46; All related studies were reviewed and analyzed&#46;</p><p id="sp0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Results&#46;</span> Many studies explicitly indicated that DILI and its progression to acute liver failure were causatively linked to endoplasmic reticulum stress and subsequently induced autophagy&#44; which protect hepatocytes during DILI&#46; LncRNA&#44; as a noncoding RNA&#44; influences the regulation of the expression of ATGs to manipulate autophagy&#46;</p><p id="sp0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Conclusions&#46;</span> This review described the recent findings on autophagy and its possible lncRNA-miRNA-associated pathways&#44; thereby providing new insights for further studies on the pathogenesis of DILI&#46;</p></span>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "f0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 426
            "Ancho" => 696
            "Tamanyo" => 64126
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">ATGs involved in the initiation of autophagy induced by endoplasmic reticulum &#40;ER&#41; stress&#46; First&#44; the ULK1-ATG13-FIP200-ATG101 complex is activated&#46; Then&#44; PtdIns3K class III complexes &#40;Beclin1-VPS15-VPS34&#41; are induced to transform phosphatidylinositol 3-phosphate &#40;PtdIns3P&#41; intensified by ATG14&#44; followed by recruitment of downstream effectors such as DFCP1 and WIPI-family&#46; ATG12-ATG5-ATG16L1 complex exerts its E3-like function and thus catalyzes LC3-I&#44; leading to LC3 cleavage by ATG4 to LC3-II&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "f0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 457
            "Ancho" => 696
            "Tamanyo" => 32139
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">ATG12-ATG5 system involved in the expansion of autophagosomes&#46; First&#44; ATG7 activates ATG12 by functioning as an E1-like enzyme&#46; Then&#44; ATG12 conjugates to ATG5 and ATG16L&#44; forming a functional complex as an E3-like enzyme&#46; Meanwhile&#44; activated ATG12 recruits ATG3&#44; which acts as an E2-like enzyme&#46; Finally&#44; LC3 conjugates to PE under the action of the complex and ATG3&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "t0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">lncRNA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Targest&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Role in autophagy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">References&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MALAT1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">miR-30a miR-101 miR-216b miR-124 miR-23b-3p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MALAT1 activates autophagy serving as a molecular sponge for miR-30a that suppresses Beclin1-dependent autophagy and miR-101&#44; RAB5A&#44; and ATG4D It also binds to miR-216b&#44; modulating autophagy It promotes autophagy by directly targeting miR-124 It induces autophagy for acting as a ceRNA for miR-23b-3p to increase the expression of ATG12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ischemic stroke&#59; glioma&#59; hepatocellular carcinoma&#59; retinoblastoma&#59; gastric cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="right" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">88</span></a>&#44; <a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">89</span></a>&#44; <a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">90</span></a>&#44; <a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">91</span></a>&#44; <a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">92</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TGFB2-OT1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">miR-3960&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TGFB2-OT1 acts as a competing endogenous RNA regulating the expression of&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vascular endothelial cell&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="right" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">85</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;FLJ11812&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">miR-4488 miR-4459&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">the miRNA targets CERS1&#44; NAT8L&#44; and LARP1&#44; which participate in autophagy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">dysfunction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">miR-188-3p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APF regulates the expression of ATG7 through miR-188-3p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="right" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">93</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HULC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">miR-6886-3p miR-6825-5p&#44; miR-6845-5p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HULC downregulates miR-6825-5p&#44; miR-6845-5p&#44; and miR-6886-3p to protect autophagy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hepatocellular carcinoma &#40;HCC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="right" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">94</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AC023115&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">miR-26a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AC023115&#46;3 acts as a competing endogenous RNA for miR-26a&#44; which has an inhibitory effect on GSK3&#226; leading to a decrease in autophagy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glioma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="right" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">95</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HNF1A-AS1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">miR-30b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HNF1A-AS1 promotes autophagy by acting as a ceRNA for miR-30b&#44; which can regulate the expression of Bcl-2 and ATG5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hepatocellular carcinoma &#40;HCC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="right" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">96</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PTENP1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">miR-17 miR-19b miR-20a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PTENP1 induces autophagy through decoying miR-17&#44; miR-19b&#44; and miR-20a&#44; which target autophagy genes as ULK1&#44; ATG7&#44; and p62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hepatocellular carcinoma &#40;HCC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="right" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PVT1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">miR-186&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PVT1 induces autophagy by targeting miR-186&#44; which decreases the expression of Atg7 and Beclin1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glioma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="right" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">97</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HOTAIR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">miR-454-3p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HOTAIR increases autophagy by inducing DNA methylation of miR-454-3p&#44; which targets STAT3 and ATG12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chondrosarcoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="right" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">98</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GAS5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">miR-21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GAS5 suppresses autophagy for acting as a negative regulator of miR-21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Osteoarthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="right" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">99</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PCGEM1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">miR-770&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PCGEM1 induces autophagy by acting as a sponge for miR-770&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Osteoarthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="right" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">100</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2031790.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">IncRNA-miRNA associated with autophagy&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bs0010"
          "bibliografiaReferencia" => array:100 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced liver injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.5858/arpa.2014-0214-RA"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Pathol Lab Med"
                        "fecha" => "2015"
                        "volumen" => "139"
                        "paginaInicial" => "876"
                        "paginaFinal" => "887"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Teschke R&#44; Frenzel C&#44; Wolff A&#44; Eickhoff A&#44; Schulze J&#46; Drug induced liver injury&#63;&#58; accuracy of diagnosis in published reports&#46; <span class="elsevierStyleItalic">Ann Hepatol</span> 2014&#59; 248-55&#46;"
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug Induced Liver Injury Network"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.27317"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2015"
                        "volumen" => "60"
                        "paginaInicial" => "1399"
                        "paginaFinal" => "1408"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug Induced Liver Injury at a Tertiary Hospital in India&#58; Etiology&#44; Clinical Features and Predictors of Mortality"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.5604/16652681.1235488"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Hepatol"
                        "fecha" => "2017"
                        "volumen" => "16"
                        "paginaInicial" => "442"
                        "paginaFinal" => "450"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced liver injury&#58; Do we know everything"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4254/wjh.v9.i10.491"
                      "Revista" => array:6 [
                        "tituloSerie" => "World J Hepatol"
                        "fecha" => "2017"
                        "volumen" => "9"
                        "paginaInicial" => "491"
                        "paginaFinal" => "502"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced liver injury&#58; recent advances in diagnosis and risk assessment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gutjnl-2016-313369"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut"
                        "fecha" => "2017"
                        "volumen" => "66"
                        "paginaInicial" => "1154"
                        "paginaFinal" => "1164"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug Induced Liver Injury&#58; Review with a Focus on Genetic Factors&#44; Tissue Diagnosis&#44; and Treatment Options"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.14218/JCTH.2015.00007"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Transl Hepatol"
                        "fecha" => "2015"
                        "volumen" => "3"
                        "paginaInicial" => "99"
                        "paginaFinal" => "108"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "CSH guidelines for the diagnosis and treatment of drug-induced liver injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12072-017-9793-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatol Int"
                        "fecha" => "2017"
                        "volumen" => "11"
                        "paginaInicial" => "221"
                        "paginaFinal" => "241"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "ACG Clinical Guideline&#58; The Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ajg.2014.131"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Gastroenterol"
                        "fecha" => "2014"
                        "volumen" => "109"
                        "paginaInicial" => "950"
                        "paginaFinal" => "966"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced liver injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Med &#40;Northfield Il&#41;"
                        "fecha" => "2016"
                        "volumen" => "38"
                        "paginaInicial" => "S44"
                        "paginaFinal" => "S48"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "NAT2 genetic polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in Chinese community population"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Hepatol"
                        "fecha" => "2012"
                        "volumen" => "11"
                        "paginaInicial" => "700"
                        "paginaFinal" => "707"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-Induced Endoplasmic Reticulum and Oxidative Stress Responses Independently Sensitize Toward TNF&#945;-Mediated Hepatotoxicity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/toxsci/kfu072"
                      "Revista" => array:6 [
                        "tituloSerie" => "Toxicol Sci"
                        "fecha" => "2014"
                        "volumen" => "140"
                        "paginaInicial" => "144"
                        "paginaFinal" => "159"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "CHOP is a critical regulator of acetaminophen-induced hepatotoxicity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2013.04.024"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2013"
                        "volumen" => "59"
                        "paginaInicial" => "495"
                        "paginaFinal" => "503"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protective neuronal induction of ATF5 in endoplasmic reticulum stress induced by status epilepticus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/brain/awt044"
                      "Revista" => array:6 [
                        "tituloSerie" => "Brain"
                        "fecha" => "2013"
                        "volumen" => "136"
                        "paginaInicial" => "1161"
                        "paginaFinal" => "1176"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Xie H&#44; Tang C-HA&#44; Song JH&#44; Mancuso A&#44; Valle JR Del&#44; Cao J&#44; Xiang Y&#44; et al&#46; IRE1&#945; RNase-dependent lipid homeostasis promotes survival in Myc-transformed cancers&#46; <span class="elsevierStyleItalic">J Clin Invest&#46;</span> Published Online First&#58; 30 January 2018&#46;"
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A current perspective of autophagosome biogenesis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/cr.2013.159"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Res"
                        "fecha" => "2014"
                        "volumen" => "24"
                        "paginaInicial" => "58"
                        "paginaFinal" => "68"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Functions of autophagy in normal and diseased liver"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4161/auto.25063"
                      "Revista" => array:6 [
                        "tituloSerie" => "Autophagy"
                        "fecha" => "2013"
                        "volumen" => "9"
                        "paginaInicial" => "1131"
                        "paginaFinal" => "1158"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autophagy in the Cellular Energetic Balance"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cmet.2011.04.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Metab"
                        "fecha" => "2011"
                        "volumen" => "13"
                        "paginaInicial" => "495"
                        "paginaFinal" => "504"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lin Haifan&#46; Induction of Autophagy&#44; a Promising Approach for Treating Liver Injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrm2621"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Mol Cell Biol"
                        "fecha" => "2009"
                        "volumen" => "10"
                        "paginaInicial" => "116"
                        "paginaFinal" => "125"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhibition of macroautophagy triggers apoptosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/MCB.25.3.1025-1040.2005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Cell Biol"
                        "fecha" => "2005"
                        "volumen" => "25"
                        "paginaInicial" => "1025"
                        "paginaFinal" => "1040"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dynamics and diversity in autophagy mechanisms&#58; lessons from yeast"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrm2708"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Mol Cell Biol"
                        "fecha" => "2009"
                        "volumen" => "10"
                        "paginaInicial" => "458"
                        "paginaFinal" => "467"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autophagy&#58; more than a nonselective pathway"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1155/2012/219625"
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Cell Biol"
                        "fecha" => "2012"
                        "volumen" => "2012"
                        "paginaInicial" => "219625"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cathepsin L&#46; A new proteinase from rat-liver lysosomes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Biochem"
                        "fecha" => "1977"
                        "volumen" => "74"
                        "paginaInicial" => "293"
                        "paginaFinal" => "301"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autophagy&#58; Renovation of Cells and Tissues"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cell.2011.10.026"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell"
                        "fecha" => "2011"
                        "volumen" => "147"
                        "paginaInicial" => "728"
                        "paginaFinal" => "741"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Opinion&#58; Autophagy&#58; dual roles in life and death"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrm1666"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Mol Cell Biol"
                        "fecha" => "2005"
                        "volumen" => "6"
                        "paginaInicial" => "505"
                        "paginaFinal" => "510"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Anding AL&#44; Baehrecke EH&#46; Autophagy in Cell Life and Cell Death&#46; In&#58; <span class="elsevierStyleItalic">Current topics in developmental biology</span> 2015&#59; 67-91&#46;"
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cell death by autophagy&#58; facts and apparent artefacts"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/cdd.2011.146"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Death Differ"
                        "fecha" => "2012"
                        "volumen" => "19"
                        "paginaInicial" => "87"
                        "paginaFinal" => "95"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autophagy inhibition due to thymidine analogues as novel mechanism leading to hepatocyte dysfunction and lipid accumulation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/QAD.0b013e32835804f9"
                      "Revista" => array:6 [
                        "tituloSerie" => "AIDS"
                        "fecha" => "2012"
                        "volumen" => "26"
                        "paginaInicial" => "1995"
                        "paginaFinal" => "2006"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI60580"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2012"
                        "volumen" => "122"
                        "paginaInicial" => "2428"
                        "paginaFinal" => "2438"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autophagy and mitophagy in the context of doxorubicin-induced cardiotoxicity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.18632/oncotarget.16944"
                      "Revista" => array:6 [
                        "tituloSerie" => "Oncotarget"
                        "fecha" => "2017"
                        "volumen" => "8"
                        "paginaInicial" => "46663"
                        "paginaFinal" => "46680"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Studying Autophagy in Zebrafish"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Cells"
                        "fecha" => "2017"
                        "volumen" => "6"
                        "paginaInicial" => "21"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Macrophage autophagy limits acute toxic liver injury in mice through down regulation of interleukin-1 &#946;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2015"
                        "volumen" => "14"
                        "paginaInicial" => "1"
                        "paginaFinal" => "14"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autophagy protects from liver injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/cdd.2013.43"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Death Differ"
                        "fecha" => "2013"
                        "volumen" => "20"
                        "paginaInicial" => "850"
                        "paginaFinal" => "851"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regulation of liver metabolism by autophagy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2015.09.042"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2015"
                        "volumen" => "150"
                        "paginaInicial" => "328"
                        "paginaFinal" => "339"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhibition of hepatocyte autophagy increases tumor necrosis factor-dependent liver injury by promoting caspase-8 activation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/cdd.2013.21"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Death Differ"
                        "fecha" => "2013"
                        "volumen" => "20"
                        "paginaInicial" => "878"
                        "paginaFinal" => "887"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1083/jcb.200412022"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cell Biol"
                        "fecha" => "2005"
                        "volumen" => "169"
                        "paginaInicial" => "425"
                        "paginaFinal" => "434"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The ontogeny of human drug-metabolizing enzymes&#58; phase II conjugation enzymes and regulatory mechanisms"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pharmacol Exp Ther"
                        "fecha" => "2002"
                        "volumen" => "300"
                        "paginaInicial" => "361"
                        "paginaFinal" => "366"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanisms of Drug Induced Liver Injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Liver Dis"
                        "fecha" => "2008"
                        "volumen" => "86"
                        "paginaInicial" => "3279"
                        "paginaFinal" => "3288"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanisms in drug-induced liver injury&#58; lessons"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/03602532.2011.602688"
                      "Revista" => array:6 [
                        "tituloSerie" => "Drug Metab Rev"
                        "fecha" => "2017"
                        "volumen" => "44"
                        "paginaInicial" => "88"
                        "paginaFinal" => "106"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "UPR&#44; autophagy and mitochondria crosstalk underlies the ER stress response"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Trends Biochem Sci"
                        "fecha" => "2015"
                        "volumen" => "13"
                        "paginaInicial" => "36"
                        "paginaFinal" => "37"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Decoding cell death signals in liver inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2013.03.033"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2013"
                        "volumen" => "59"
                        "paginaInicial" => "583"
                        "paginaFinal" => "594"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autophagy is involved in en-doplasmic reticulum stress induced cell death of rat hepato-cytes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Surg Res 2013"
                        "fecha" => "2014"
                        "volumen" => "6"
                        "paginaInicial" => "1"
                        "paginaFinal" => "16"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intracellular Signaling Mechanisms of Acetaminophen-Induced Liver Cell Death"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/toxsci/kfi336"
                      "Revista" => array:6 [
                        "tituloSerie" => "Toxicol Sci"
                        "fecha" => "2006"
                        "volumen" => "89"
                        "paginaInicial" => "31"
                        "paginaFinal" => "41"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acetaminophen-induced acute liver failure&#58; Results of a United States multicenter&#44; prospective study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.20948"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2005"
                        "volumen" => "42"
                        "paginaInicial" => "1364"
                        "paginaFinal" => "1372"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Adi-ponectin protects against acetaminophen-induced mito-chondrial dysfunction and acute liver injury by promoting autophagy in mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2014.05.033"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2014"
                        "volumen" => "61"
                        "paginaInicial" => "825"
                        "paginaFinal" => "831"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Activation of autophagy protects against acetaminophen-in-duced hepatotoxicity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.24690"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2012"
                        "volumen" => "55"
                        "paginaInicial" => "222"
                        "paginaFinal" => "232"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF&#945;-mediated hepatotoxicity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/toxsci/kfu072"
                      "Revista" => array:6 [
                        "tituloSerie" => "Toxicol Sci"
                        "fecha" => "2014"
                        "volumen" => "140"
                        "paginaInicial" => "144"
                        "paginaFinal" => "159"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cytochrome P450s&#58; mechanisms and biological implications in drug metabolism and its interaction with oxidative stress"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Drug Metab"
                        "fecha" => "2014"
                        "volumen" => "15"
                        "paginaInicial" => "719"
                        "paginaFinal" => "742"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "49&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Microsomal oxidative damage promoted by acetaminophen metabolism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Toxicol Vitr"
                        "fecha" => "2011"
                        "volumen" => "25"
                        "paginaInicial" => "1310"
                        "paginaFinal" => "1313"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "50&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Suppression of autophagy dysregulates the antioxidant response and causes premature senescence of melanocytes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/jid.2014.439"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Invest Dermatol"
                        "fecha" => "2015"
                        "volumen" => "135"
                        "paginaInicial" => "1348"
                        "paginaFinal" => "1357"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "51&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.plipres.2012.10.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Prog Lipid Res"
                        "fecha" => "2013"
                        "volumen" => "52"
                        "paginaInicial" => "165"
                        "paginaFinal" => "174"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "52&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacological Promotion of Autophagy Alleviates Steatosis and Injury in Alcoholic and Non-alcoholic Fatty Liver Conditions in Mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2013.01.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2013"
                        "volumen" => "58"
                        "paginaInicial" => "993"
                        "paginaFinal" => "999"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "53&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Alerting E&#46; Autophagy&#63;&#58; process and function&#46; <span class="elsevierStyleItalic">GENES Dev</span> 2007&#59; 2861-73&#46;"
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "54&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1083/jcb.200803137"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cell Biol"
                        "fecha" => "2008"
                        "volumen" => "182"
                        "paginaInicial" => "685"
                        "paginaFinal" => "701"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "55&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "3D tomography reveals connections between the phagophore and endoplasmic reticulum"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Autophagy"
                        "fecha" => "2009"
                        "volumen" => "5"
                        "paginaInicial" => "1180"
                        "paginaFinal" => "1185"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "56&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ncb1991"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Cell Biol"
                        "fecha" => "2009"
                        "volumen" => "11"
                        "paginaInicial" => "1433"
                        "paginaFinal" => "1437"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "57&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Autophagy"
                        "fecha" => "2010"
                        "volumen" => "6"
                        "paginaInicial" => "764"
                        "paginaFinal" => "776"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "58&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "How to control self-digestion&#58; transcriptional&#44; post- transcriptional&#44; and post-translational regulation of autophagy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Trends Cell Biol"
                        "fecha" => "2014"
                        "volumen" => "25"
                        "paginaInicial" => "367"
                        "paginaFinal" => "402"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "59&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regulation of autophagy&#58; Modulation of the size and number of autophagosomes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "FEBS Lett"
                        "fecha" => "2009"
                        "volumen" => "42"
                        "paginaInicial" => "115"
                        "paginaFinal" => "125"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "60&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autophagy signal transduction by ATG proteins&#58; From hierarchies to networks"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00018-015-2034-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Mol Life Sci"
                        "fecha" => "2015"
                        "volumen" => "72"
                        "paginaInicial" => "4721"
                        "paginaFinal" => "4757"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "61&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of autophagy during the early neonatal starvation period"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature03029"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2004"
                        "volumen" => "432"
                        "paginaInicial" => "1032"
                        "paginaFinal" => "1036"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "62&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Historical landmarks of autophagy research"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Nat Publ Gr"
                        "fecha" => "2013"
                        "volumen" => "24"
                        "paginaInicial" => "9"
                        "paginaFinal" => "23"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "63&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Expression of the au-tophagy substrate SQSTM1&#47;p62 is restored during prolonged starvation depending on transcriptional upregulation and autophagy-derived amino acids"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4161/auto.27344"
                      "Revista" => array:6 [
                        "tituloSerie" => "Autophagy"
                        "fecha" => "2014"
                        "volumen" => "10"
                        "paginaInicial" => "431"
                        "paginaFinal" => "441"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "64&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhibition of soluble epoxide hydrolase modulates inflammation and autophagy in obese adipose tissue and liver&#58; Role for omega-3 epoxides"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.1422590112"
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci"
                        "fecha" => "2015"
                        "volumen" => "112"
                        "paginaInicial" => "536"
                        "paginaFinal" => "541"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "65&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nrf2 Promotes the Development of Fibrosis and Tumorigenesis in Mice with Defective Hepatic Autophagy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2014.04.043"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2015"
                        "volumen" => "61"
                        "paginaInicial" => "617"
                        "paginaFinal" => "625"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "66&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Transcriptional regulation of autophagy by an FXR&#47;CREB axis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature13949"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2015"
                        "volumen" => "516"
                        "paginaInicial" => "108"
                        "paginaFinal" => "111"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "67&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The noncoding RNA revolution-trashing old rules to forge new ones"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cell.2014.03.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell"
                        "fecha" => "2014"
                        "volumen" => "157"
                        "paginaInicial" => "77"
                        "paginaFinal" => "94"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "68&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Massive rearrangements of cellular MicroRNA signatures are key drivers of hepatocyte dedifferentiation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.28780"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2016"
                        "volumen" => "64"
                        "paginaInicial" => "1743"
                        "paginaFinal" => "1756"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "69&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long noncoding RNAs in kidney and cardiovascular diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrneph.2016.51"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Nephrol"
                        "fecha" => "2016"
                        "volumen" => "12"
                        "paginaInicial" => "360"
                        "paginaFinal" => "373"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "70&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature21034"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2016"
                        "volumen" => "541"
                        "paginaInicial" => "228"
                        "paginaFinal" => "232"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "71&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The evolution of lncRNA repertoires and expression patterns in tetrapods"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature12943"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2014"
                        "volumen" => "505"
                        "paginaInicial" => "635"
                        "paginaFinal" => "640"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "72&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "MicroRNAs in Drug-induced Liver Injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.14218/JCTH.2014.00015"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Transl Hepatol"
                        "fecha" => "2014"
                        "volumen" => "2"
                        "paginaInicial" => "162"
                        "paginaFinal" => "169"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "73&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Structural bioinformatics A comprehensive benchmark of RNA - RNA interaction prediction tools for all domains of life"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/bioinformatics/btw728"
                      "Revista" => array:6 [
                        "tituloSerie" => "Bioinformatics"
                        "fecha" => "2017"
                        "volumen" => "33"
                        "paginaInicial" => "988"
                        "paginaFinal" => "996"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "74&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The noncoding RNA revolution - Trashing old rules to forge new ones"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cell.2014.03.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell"
                        "fecha" => "2014"
                        "volumen" => "157"
                        "paginaInicial" => "77"
                        "paginaFinal" => "94"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "75&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long Noncoding RNAs with Enhancer-like Function in Human Cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cell.2010.09.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell"
                        "fecha" => "2010"
                        "volumen" => "143"
                        "paginaInicial" => "46"
                        "paginaFinal" => "58"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "76&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Characterization of the structure&#44; function&#44; and mechanism of B2 RNA&#44; an ncR-NA repressor of RNA polymerase II transcription"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1261/rna.310307"
                      "Revista" => array:6 [
                        "tituloSerie" => "RNA"
                        "fecha" => "2007"
                        "volumen" => "13"
                        "paginaInicial" => "583"
                        "paginaFinal" => "596"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "77&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of onco-genic transcription factor B-MYB"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pgen.1003368"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS Genet"
                        "fecha" => "2013"
                        "volumen" => "9"
                        "paginaInicial" => "e1003368"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "78&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The multilayered complexity of ceRNA crosstalk and competition"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature12986"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2014"
                        "volumen" => "505"
                        "paginaInicial" => "344"
                        "paginaFinal" => "352"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            78 => array:3 [
              "identificador" => "bib0395"
              "etiqueta" => "79&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ncomms7779"
                      "Revista" => array:5 [
                        "tituloSerie" => "Nat Commun"
                        "fecha" => "2015"
                        "volumen" => "6"
                        "paginaInicial" => "6779"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            79 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "80&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identification of a novel MTOR activator and discovery of a competing endogenous RNA regulating autophagy in vascular endothelial cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4161/auto.28363"
                      "Revista" => array:6 [
                        "tituloSerie" => "Autophagy"
                        "fecha" => "2014"
                        "volumen" => "10"
                        "paginaInicial" => "957"
                        "paginaFinal" => "971"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            80 => array:3 [
              "identificador" => "bib0405"
              "etiqueta" => "81&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Suppression of hepatocellular carcinoma by baculovirus-mediated expression of long non-coding RNA PTENP1 and MicroRNA regulation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.biomaterials.2014.12.023"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biomaterials"
                        "fecha" => "2015"
                        "volumen" => "44"
                        "paginaInicial" => "71"
                        "paginaFinal" => "81"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            81 => array:3 [
              "identificador" => "bib0410"
              "etiqueta" => "82&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The long noncoding RNA HOTAIR activates autophagy by upregulating ATG3 and ATG7 in hepatocellular carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1039/c6mb00114a"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol BioSyst"
                        "fecha" => "2016"
                        "volumen" => "12"
                        "paginaInicial" => "2605"
                        "paginaFinal" => "2612"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            82 => array:3 [
              "identificador" => "bib0415"
              "etiqueta" => "83&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "lncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Nat Cell Biol"
                        "fecha" => "2015"
                        "volumen" => "10"
                        "paginaInicial" => "552"
                        "paginaFinal" => "554"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            83 => array:3 [
              "identificador" => "bib0420"
              "etiqueta" => "84&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Down regulated lncRNA MEG3 eliminates mycobacteria in macrophages via autophagy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/srep19416"
                      "Revista" => array:5 [
                        "tituloSerie" => "Sci Rep"
                        "fecha" => "2016"
                        "volumen" => "6"
                        "paginaInicial" => "19416"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            84 => array:3 [
              "identificador" => "bib0425"
              "etiqueta" => "85&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A new microRNA signal pathway regulated by long noncoding RNA TGFB2-OT1 in autophagy and inflammation of vascular endothelial cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/15548627.2015.1106663"
                      "Revista" => array:6 [
                        "tituloSerie" => "Autophagy"
                        "fecha" => "2015"
                        "volumen" => "11"
                        "paginaInicial" => "2172"
                        "paginaFinal" => "2183"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            85 => array:3 [
              "identificador" => "bib0430"
              "etiqueta" => "86&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Down-regulation of Risa improves insulin sensitivity by enhancing autophagy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1096/fj.201500058R"
                      "Revista" => array:6 [
                        "tituloSerie" => "FASEB J"
                        "fecha" => "2016"
                        "volumen" => "30"
                        "paginaInicial" => "3133"
                        "paginaFinal" => "3145"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            86 => array:3 [
              "identificador" => "bib0435"
              "etiqueta" => "87&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "PCGEM1 stimulates proliferation of osteoarthritic synoviocytes by acting as a sponge for miR-770"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jor.23046"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Orthop Res"
                        "fecha" => "2016"
                        "volumen" => "34"
                        "paginaInicial" => "412"
                        "paginaFinal" => "418"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            87 => array:3 [
              "identificador" => "bib0440"
              "etiqueta" => "88&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Down-Regulation of Lncrna MALAT1 Attenuates Neuronal Cell Death Through Suppressing Beclin1-Dependent Autophagy by Regulating Mir-30a in Cerebral Ischemic Stroke"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000480337"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Physiol Biochem"
                        "fecha" => "2017"
                        "volumen" => "43"
                        "paginaInicial" => "182"
                        "paginaFinal" => "194"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            88 => array:3 [
              "identificador" => "bib0445"
              "etiqueta" => "89&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1&#44; RAB5A and ATG4D expression in glioma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbrc.2017.08.070"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biochem Biophys Res Commun"
                        "fecha" => "2017"
                        "volumen" => "492"
                        "paginaInicial" => "480"
                        "paginaFinal" => "486"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            89 => array:3 [
              "identificador" => "bib0450"
              "etiqueta" => "90&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The HIF-2&#945;-MALAT1-miR-216b axis regulates multi-drug resistance of hepatocellular carcinoma cells via modulating autophagy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbrc.2016.08.065"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biochem Biophys Res Commun"
                        "fecha" => "2016"
                        "volumen" => "478"
                        "paginaInicial" => "1067"
                        "paginaFinal" => "1073"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            90 => array:3 [
              "identificador" => "bib0455"
              "etiqueta" => "91&#46;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Huang J&#44; Yang Y&#44; Fang F&#44; Liu K&#46; MALAT1 modulates the autophagy of retinoblastoma cell through miR-124-mediated stx17 regulation&#46; <span class="elsevierStyleItalic">J Cell Biochem</span> Published Online First&#58; 19 January 2018&#46;"
                ]
              ]
            ]
            91 => array:3 [
              "identificador" => "bib0460"
              "etiqueta" => "92&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long noncoding RNA MALAT1 regulates autophagy associated chemoresistance via miR-23b-3p sequestration in gastric cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s12943-017-0743-3"
                      "Revista" => array:5 [
                        "tituloSerie" => "Mol Cancer"
                        "fecha" => "2017"
                        "volumen" => "16"
                        "paginaInicial" => "174"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            92 => array:3 [
              "identificador" => "bib0465"
              "etiqueta" => "93&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ncomms7779"
                      "Revista" => array:5 [
                        "tituloSerie" => "Nat Commun"
                        "fecha" => "2015"
                        "volumen" => "6"
                        "paginaInicial" => "6779"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            93 => array:3 [
              "identificador" => "bib0470"
              "etiqueta" => "94&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "LncRNA HULC triggers autophagy via stabilizing Sirt1 and attenuates the chemosensitivity of HCC cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/onc.2016.521"
                      "Revista" => array:6 [
                        "tituloSerie" => "Oncogene"
                        "fecha" => "2017"
                        "volumen" => "36"
                        "paginaInicial" => "3528"
                        "paginaFinal" => "3540"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            94 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "95&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long non-coding RNA AC023115&#46;3 suppresses chemoresistance of glioblastoma by reducing autophagy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [ …7]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Biochim Biophys Acta"
                        "fecha" => "2017"
                        "volumen" => "1864"
                        "paginaInicial" => "1393"
                        "paginaFinal" => "1404"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            95 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "96&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long non-coding RNA HNF1A-AS1 functioned as an oncogene and autophagy promoter in hepatocellular carcinoma through sponging hsa-miR-30b-5p"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbrc.2016.04.054"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biochem Biophys Res Commun"
                        "fecha" => "2016"
                        "volumen" => "473"
                        "paginaInicial" => "1268"
                        "paginaFinal" => "1275"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            96 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "97&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "PVT1 affects growth of glioma microvascular endothelial cells by negatively regulating miR-186"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Tumor Biol"
                        "fecha" => "2017"
                        "volumen" => "39"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            97 => array:3 [
              "identificador" => "bib0490"
              "etiqueta" => "98&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Knockdown of long non-coding RNA HOTAIR increases miR-454-3p by targeting Stat3 and Atg12 to inhibit chondrosarcoma growth"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/cddis.2017.31"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cell Death Dis"
                        "fecha" => "2017"
                        "volumen" => "8"
                        "paginaInicial" => "e2605"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            98 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "99&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A long non-coding RNA&#44; GAS5&#44; plays a critical role in the regulation of miR-21 during osteoarthritis"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jor.22718"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Orthop Res"
                        "fecha" => "2014"
                        "volumen" => "32"
                        "paginaInicial" => "1628"
                        "paginaFinal" => "1635"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            99 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "100&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "PCGEM1 stimulates proliferation of osteoarthritic synoviocytes by acting as a sponge for miR-770"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jor.23046"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Orthop Res"
                        "fecha" => "2016"
                        "volumen" => "34"
                        "paginaInicial" => "412"
                        "paginaFinal" => "418"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/16652681/0000001700000003/v1_201905160920/S1665268119301929/v1_201905160920/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "77721"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original Article"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/16652681/0000001700000003/v1_201905160920/S1665268119301929/v1_201905160920/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119301929?idApp=UINPBA00004N"
]

Article information

ISSN: 16652681
Original language: English

DOI:10.5604/01.3001.0011.7381

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	3	1	4
2024 October	33	10	43
2024 September	33	5	38
2024 August	22	9	31
2024 July	33	4	37
2024 June	22	5	27
2024 May	40	6	46
2024 April	48	9	57
2024 March	40	8	48
2024 February	39	8	47
2024 January	30	8	38
2023 December	24	14	38
2023 November	21	7	28
2023 October	21	7	28
2023 September	22	8	30
2023 August	18	6	24
2023 July	11	2	13
2023 June	31	5	36
2023 May	65	4	69
2023 April	52	4	56
2023 March	57	2	59
2023 February	38	6	44
2023 January	14	4	18
2022 December	14	7	21
2022 November	22	6	28
2022 October	14	10	24
2022 September	15	8	23
2022 August	15	5	20
2022 July	12	9	21
2022 June	11	7	18
2022 May	18	11	29
2022 April	10	7	17
2022 March	19	10	29
2022 February	25	10	35
2022 January	45	4	49
2021 December	28	9	37
2021 November	38	15	53
2021 October	11	8	19
2021 September	9	13	22
2021 August	6	4	10
2021 July	6	14	20
2021 June	11	7	18
2021 May	19	10	29
2021 April	64	8	72
2021 March	29	12	41
2021 February	20	13	33
2021 January	37	15	52
2020 December	33	5	38
2020 November	32	3	35
2020 October	23	10	33
2020 September	19	10	29
2020 August	14	7	21
2020 July	14	5	19
2020 June	10	5	15
2020 May	10	9	19
2020 April	12	3	15
2020 March	12	1	13
2020 February	8	6	14
2020 January	10	3	13
2019 December	8	5	13
2019 November	8	2	10
2019 October	14	3	17
2019 September	10	5	15
2019 August	5	1	6
2019 July	15	4	19
2019 June	13	2	15
2019 May	8	11	19

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter