LncRNA MAGI2-AS3 is downregulated in the distant recurrence of hepatocellular carcinoma after surgical resection and affects migration and invasion via ROCK2

array:24 ["pii" => "S1665268120300466" "issn" => "16652681" "doi" => "10.1016/j.aohep.2020.04.007" "estado" => "S300" "fechaPublicacion" => "2020-09-01" "aid" => "205" "copyright" => "Fundación Clínica Médica Sur, A.C." "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2020;19:535-40" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:18 [ "pii" => "S1665268120300818" "issn" => "16652681" "doi" => "10.5604/01.3001.0012.2246" "estado" => "S300" "fechaPublicacion" => "2020-09-01" "aid" => "234" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2020;19:541-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Efficacy and safety of basiliximab as initial immunosuppression in liver transplantation: A single center study" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "541" "paginaFinal" => "545" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1261 "Ancho" => 1583 "Tamanyo" => 71064 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Comparison of survival between both groups." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Mohamed Hashim, Ayman Alsebaey, Amr Ragab, Hossam Eldeen Soliman, Imam Waked" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Mohamed" "apellidos" => "Hashim" ] 1 => array:2 [ "nombre" => "Ayman" "apellidos" => "Alsebaey" ] 2 => array:2 [ "nombre" => "Amr" "apellidos" => "Ragab" ] 3 => array:2 [ "nombre" => "Hossam Eldeen" "apellidos" => "Soliman" ] 4 => array:2 [ "nombre" => "Imam" "apellidos" => "Waked" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268120300818?idApp=UINPBA00004N" "url" => "/16652681/0000001900000005/v5_202012011817/S1665268120300818/v5_202012011817/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268120300478" "issn" => "16652681" "doi" => "10.1016/j.aohep.2020.04.008" "estado" => "S300" "fechaPublicacion" => "2020-09-01" "aid" => "206" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2020;19:530-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Propranolol for infantile hepatic hemangioendothelioma: Clinical evaluation of drug efficacy and safety using a single-center patient cohort" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "530" "paginaFinal" => "534" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1427 "Ancho" => 3333 "Tamanyo" => 256541 ] ] "descripcion" => array:1 [ "en" => "Three-day-old female with IHHE diagnosed by enhanced MRI. (A, B) Magnetic Resonance Imaging revealing IHHE lesion before oral propranolol treatment. (C) Ultrasound examination shows a lesion that decreased by about 100% in volume, after two months of oral propranolol treatment." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ruicheng Tian, Yu Liang, Jing Wang, Yuhua Shan, Hongxiang Gao, Lei Zhang, Chenjie Xie, Jingjing Li, Min Xu, Song Gu" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Ruicheng" "apellidos" => "Tian" ] 1 => array:2 [ "nombre" => "Yu" "apellidos" => "Liang" ] 2 => array:2 [ "nombre" => "Jing" "apellidos" => "Wang" ] 3 => array:2 [ "nombre" => "Yuhua" "apellidos" => "Shan" ] 4 => array:2 [ "nombre" => "Hongxiang" "apellidos" => "Gao" ] 5 => array:2 [ "nombre" => "Lei" "apellidos" => "Zhang" ] 6 => array:2 [ "nombre" => "Chenjie" "apellidos" => "Xie" ] 7 => array:2 [ "nombre" => "Jingjing" "apellidos" => "Li" ] 8 => array:2 [ "nombre" => "Min" "apellidos" => "Xu" ] 9 => array:2 [ "nombre" => "Song" "apellidos" => "Gu" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268120300478?idApp=UINPBA00004N" "url" => "/16652681/0000001900000005/v5_202012011817/S1665268120300478/v5_202012011817/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "LncRNA MAGI2-AS3 is downregulated in the distant recurrence of hepatocellular carcinoma after surgical resection and affects migration and invasion via ROCK2" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "535" "paginaFinal" => "540" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Gang Fang, Jianjun Wang, Xiaowei Sun, Rui Xu, Xiaolong Zhao, Liming Shao, Chengjing Sun, Yanhua Wang" "autores" => array:8 [ 0 => array:3 [ "nombre" => "Gang" "apellidos" => "Fang" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Jianjun" "apellidos" => "Wang" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Xiaowei" "apellidos" => "Sun" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Rui" "apellidos" => "Xu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Xiaolong" "apellidos" => "Zhao" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 5 => array:3 [ "nombre" => "Liming" "apellidos" => "Shao" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 6 => array:3 [ "nombre" => "Chengjing" "apellidos" => "Sun" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 7 => array:4 [ "nombre" => "Yanhua" "apellidos" => "Wang" "email" => array:1 [ 0 => "fbfjhr3398305@126.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Radiology, Jimo District Hospital of Traditional Chinese Medicine, Qingdao 266200, Shandong Province, China" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Radiology, Traditional Chinese Medicine Medical Hospital of Zhucheng 262200, Shandong Province, China" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Qingdao Commercial Staff Hospital, Qingdao, Shandong Province, China" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "The Interventional Medicine Center the Affiliated Hospital of Qingdao University China, Qingdao 266003, Shandong Province, China" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author at:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2377 "Ancho" => 2833 "Tamanyo" => 399550 ] ] "descripcion" => array:1 [ "en" => "Expression levels of MAGI2-AS3 were increased after resection of tumors and increased in HCC patients with distant recurrence during follow-up. Expression levels of MAGI2-AS3 in HCC patients were measured by qPCR at 3 time points – pre-treatment, discharge and follow-up. Plasma levels of MAGI2-AS3 were compared between pretreatment levels and the levels of the day of discharge (A). During follow-up, distance recurrence (combined with local recurrence in most cases) was observed in 27 cases, local recurrence (no distant recurrence) was observed in 22 cases, and the rest showed no recurrence. Comparisons of plasma levels of MAGI2-AS3 between discharge level and follow-up level were performed in patients with distant recurrence (B) patients with local recurrence (C) and patients with non-recurrence (D), (*, p<0.05)." ] ] ] "textoCompleto" => "1IntroductionAs the major subtype of liver cancer, hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortalities, and its prevalence rate ranks the fifth place among all types of cancer <a class="elsevierStyleCrossRef" href="#bib0105">[1]</a>. Even with the efforts that have been made on cancer prevention, the incidence of HCC still showed an increasing trend in many countries, such as China <a class="elsevierStyleCrossRef" href="#bib0110">[2]</a>. At present, effective therapeutic approaches for HCC patients at advanced stages are still lacking <a class="elsevierStyleCrossRefs" href="#bib0115">[3,4]</a>. Most HCC patients diagnosed at early stages are promising candidates for surgical resection, which is the only radical therapy <a class="elsevierStyleCrossRef" href="#bib0125">[5]</a>. Whereas, recurrence with inevitably occurs in many cases, leading to poor prognosis <a class="elsevierStyleCrossRef" href="#bib0130">[6]</a>.Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the major risk factors for HCC <a class="elsevierStyleCrossRefs" href="#bib0135">[7,8]</a>. However, the infection itself is not sufficient to initiate HCC, and multiple signaling pathways are also involved <a class="elsevierStyleCrossRefs" href="#bib0135">[7,8]</a>. Rho associated coiled-coil containing protein kinase 2 (ROCK2) is a critical regulator of actomyosin cytoskeleton and plays regulatory roles in motility and invasion of cancer cells <a class="elsevierStyleCrossRef" href="#bib0145">[9]</a>. Inhibition of the expression of ROCK2 provides new insights into cancer treatment <a class="elsevierStyleCrossRef" href="#bib0145">[9]</a>. ROCK2 can be regulated by certain long (>200nt) non-coding RNAs (lncRNAs) <a class="elsevierStyleCrossRef" href="#bib0150">[10]</a>, which participate in cancer biology mainly through the regulation of gene expression <a class="elsevierStyleCrossRef" href="#bib0155">[11]</a>. It is known that Fas may regulate the ROCK signaling <a class="elsevierStyleCrossRef" href="#bib0160">[12]</a>. A recent study showed that a novel lncRNA MAGI2-AS3 regulated Fas to suppress breast cancer <a class="elsevierStyleCrossRef" href="#bib0165">[13]</a>. Therefore, MAGI2-AS3 may also have crosstalk with the ROCK signaling. This study explored the interaction between MAGI2-AS3 and ROCK2 in HCC.2Materials and methods2.1Research subjectsThe present study selected 68 HCC patients (40 males and 28 females; age range from 33 to 67 years old; mean age 49.9±6.3 years old) selected from 233 HCC patients admitted by the affiliate hospital of Qingdao University between April 2013 and January 2016. Inclusion criteria: (1) newly diagnosed HCC cases; (2) no therapies were performed; (3) early stage (Stage1, n=28; stage 2, n=40) HCC suitable for surgical resection. Exclusion criteria: (1) recurrent HCC; (2) history of malignancies; (3) with initiated therapies. During the same time period, 68 healthy volunteers (40 males and 28 females; age range from 34 to 68 years old; mean age 49.5±6.0 years old) were also enrolled. All HCC patients and healthy volunteers signed the informed consent. This study was approved by the Ethics Committee of aforementioned hospital.2.2Plasma, treatment and a 3-year follow-upBlood (5ml) was extracted from each patient and healthy volunteer before any therapies. Patients received surgical resection combined with different doses of chemotherapies and radiotherapies according to the conditions of the patients. Blood (5ml) was also extracted on the day of discharge. After discharge, all patients were followed-up for 3 years to record the recurrence. During the follow-up, same amount of blood was extract on the day of diagnosis of recurrence or at the end of follow-up (in cases with no recurrence observed). All blood samples were centrifuged in EDTA tubes at room temperature for 14min to collect plasma (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>2.3Cell lines and cell cultureHep3B and MHCC97-H (ATCC, USA) cells were used, which have high metastasis capacity. Cells were cultivated in RPMI-1640 medium (10% FBS) under the conditions of 5% CO2 and 37°C. MAGI2-AS3 and ROCK2 expression vectors were established using pcDNA3.1 vector (RIBOBIO, Guangzhou, China) as the backbone. Hep3B and MHCC97-H cells were collected at confluence of 70–80%, and 105 cells were transfected with 10nM MAGI2-AS3 and ROCK2 expression vector or 10nM pcDNA3.1 (negative control, NC) using lipofectamine 2000 (Invitrogen, USA). The interval between cell transfection and subsequent experiment was 24h. Hep3B and MHCC97-H cells with no transfections were used as the Control (C).2.4RNA extractions and qPCRTrizol reagent (Invitrogen, USA) was used to extract total RNAs. In brief, 0.4ml Trizol was mixed with 105 H1993 or H1581 cells or 0.1ml plasma, followed by centrifugation and ethanol participation. All RNA samples were digested with DNase I, followed by reverse transcription using the MMLV Reverse Transcriptase (Lucigen, USA). All qPCR mixtures were prepared using the QuantiTect SYBR Green PCR Kit (Qiagen, Shanghai, China). The expression levels of MAGI2-AS3 and ROCK2 were determined with GAPDH as endogenous control. The following primer sequences were used: ROCK2 forward: 5′-CTA GGCCGG GCG AAG-3 and reverse 5′-TCC AGC TTC CTC TGA CGAC-3′; MAGI2-AS3 forward: 5′-CACCTTGCTTGACAACTTGA-3′ and reverse: 5′-CATTACAGCTCGGCTACTGC-3′; GAPDH forward:5′-AAG GTG AAG GTC GGA GTCAA-3′ and reverse: 5′-AAT GAA GGG GTC ATT GAT GG-3. All PCR reactions were prepared in triplicate manner and 2−ΔΔCT method was used to perform all data normalization.2.5Cell migration and invasion analysisHep3B and MHCC97-H cells were harvested and 3×104 cells were mixed with RPMI-1640 medium (1% FBS) to prepare single cell suspensions. Cells were transferred to Transwell upper chamber, and each transfection group (C, NC, overexpression) included 3 replicated wells. Before the invasion assay, Matrigel (356234, Millipore, USA) was used to coat membrane to mimic in vivo invasion barrier. Transwell lower chamber was added with RPMI-1640 medium (20% FBS). Cells were cultivated for 12h under the conditions of 5% CO2 and 37°C. After staining using 1% crystal violet (Sigma–Aldrich, USA) at 22°C for 18min, a light microscope was used to count invading and migrating cells.2.6Western blot analysisHep3B or MHCC97-H cells were harvested and counted, and 105 cells were mixed with 0.6ml RIPA solution (RIBOBIO, Guangzhou, China) to extract total proteins. Protein samples were quantified and denatured in boiled water for 6min, followed by electrophoresis using 12% SDS-PAGE gel. Gel transfer (PVDF membrane) and blocking (2h in 5% non-fate milk) were then performed, followed by incubation with primary antibodies of rabbit polyclonal ROCK2 (1:900, ab71598, Abcam), Caspase 3(1:900, ab13847, Abcam) and GAPDH antibody (1: 900, ab37168, Abcam) at 4°C for 12h. After that, membranes were further incubated with Goat anti-Rabbit IgG (H+L) HRP secondary antibody (Thermo Fisher Scientific, Inc) at 22°C for 2h. ECL (Sigma–Aldrich, USA) was used to develop signals. Gray values were normalized using the Image J v1.46 software.2.7Statistical analysisAll data analyses were performed using the mean values of 3 biological replicates. Differences between two groups (HCC vs. Control) were explored using unpaired t test. Differences among different cell transfection groups were explored by ANOVA (one-way) and Tukey test. ROC curve was used to analyze the potentials of MAGI2-AS3 in the diagnosis of HCC. In ROC curve, true positive cases were HCC patients and true negative cases were healthy volunteers. p<0.05 was considered as statistically significant.3Results3.1MAGI2-AS3 was downregulated in HCC and showed diagnostic valuesThe levels of MAGI2-AS3 in plasma of two groups of participants (HCC patients and the Control) were measured by qPCR. The results showed that the expression levels of MAGI2-AS3 were significantly lower in HCC patients compared to that in the Control group (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A, p<0.05). ROC curve was used to analyze the potentials of MAGI2-AS3 in the diagnosis of HCC. In ROC curve, true positive cases were HCC patients and true negative cases were healthy volunteers. As shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B, the area under the curve was 0.9138, with 95% confidence interval of 0.8701–0.9575 and a standard error of 0.02231, which indicated that the diagnosis model was reliable.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>3.2The expression levels of MAGI2-AS3 were increased after resection of tumors and increased in HCC patients with distant recurrence during follow-upThe expression levels of MAGI2-AS3 in plasma of HCC patients were measured by qPCR at 3 time points, including pre-treatment, discharge and the follow-up. Compared to pretreatment, the expression levels of MAGI2-AS3 were increased on the day of discharge (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A, p<0.05). During follow-up, distance recurrence (combined with local recurrence in most cases) was observed in 27 cases, local recurrence (no distant recurrence) was observed in 22 cases, and the rest showed no recurrence. The expression levels of MAGI2-AS3 were significantly downregulated in patients with distant recurrence compared to that on the day of discharge (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B, p<0.05), but not in patients with local recurrence (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>C) or non-recurrence (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>D).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>3.3MAGI2-AS3 downregulated ROCK2 in HCC cellsHep3B and MHCC97-H cells were transfected with MAGI2-AS3 and ROCK2 expression vectors, with their cell viability and transfection rate shown in <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>A. Compared to C and NC controls, the expression levels of MAGI2-AS3 and ROCK2 were significantly increased at 24h post-transfections (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>B, p<0.05). In addition, overexpression of MAGI2-AS3 mediated the downregulation of ROCK2 (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>C, p<0.05) at both RNA and protein levels, while the expression of MAGI2-AS3 was not affected by overexpression of ROCK2 (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>D).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>3.4Overexpression of MAGI2-AS3 mediated the inhibition of HCC cell invasion, migration and apoptosis through ROCK2Cell invasion and migration assay showed that, compared to C and NC groups, overexpression of MAGI2-AS3 led to decreased cell invasion (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>A) and migration (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>B) rate in Hep3B and MHCC-97H cells, while ROCK2 played an opposite role and attenuated the effects of overexpression of MAGI2-AS3 (p<0.05). Flow cytometry demonstrated that overexpression of MAGI2-AS3 could induce HCC cell death while the effects were attenuated by the overexpression of ROCK2. In consistent with the apoptosis results, caspase3 splicing was activated by MAGI2-AS3 due to the decreased expression levels of total caspase3, while ROCK2 played the opposite role (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>C).<elsevierMultimedia ident="fig0020"></elsevierMultimedia>4DiscussionIn this study we detected the expression of MAGI2-AS3 in HCC. We found that MAGI2-AS3 was downregulated in HCC patients and might participate in distant recurrence of HCC after surgery by regulating invasion and migration of cancer cells through the interactions with ROCK2.MAGI2-AS3 was closely related to cell proliferation, invasion and migration in breast cancer and bladder cancer <a class="elsevierStyleCrossRefs" href="#bib0165">[13,14]</a>. In breast cancer, MAGI2-AS3 suppresses cancer cell proliferation and induces cancer cell apoptosis by activating the Fas/FasL signaling pathway <a class="elsevierStyleCrossRef" href="#bib0165">[13]</a>. In bladder cancer, MAGI2-AS3 sponges miR-15b-5p to upregulate tumor suppressive CCDC19, thereby inhibiting the growth of cancer cell <a class="elsevierStyleCrossRef" href="#bib0170">[14]</a>. In our study, we observed the downregulation of MAGI2-AS3 in HCC. In addition, inhibited invasion and migration of cancer cells were observed after the overexpression of MAGI2-AS3. Thus, MAGI2-AS3 also played a tumor suppressive role in HCC, which is consistent with previous studies.Compared to local recurrence, distant cancer recurrence is more aggressive <a class="elsevierStyleCrossRefs" href="#bib0175">[15,16]</a>. A recent study showed that the total recurrence rate of HCC patients after chemoembolization within 1 year is 68.5% <a class="elsevierStyleCrossRef" href="#bib0180">[16]</a>, and a considerable portion of recurrent HCC patients developed distant recurrence. Among the 68 patients included in this study, 49 of them (72.1%) developed recurrence within 3 years after discharge. We observed that MAGI2-AS3 was upregulated after surgical resection and downregulated after distant recurrence but not local recurrence. Therefore, monitoring the expression of MAGI2-AS3 may provide insights into the prediction of treatment outcomes of HCC after surgery.Cancer cell invasion and migration play pivotal roles in cancer distant recurrence <a class="elsevierStyleCrossRef" href="#bib0185">[17]</a>. In the present study, we showed that MAGI2-AS3 in HCC cells can inhibit the expression of ROCK2, which is highly expressed in HCC tissues <a class="elsevierStyleCrossRef" href="#bib0190">[18]</a> and promotes cancer cell motility and invasion <a class="elsevierStyleCrossRef" href="#bib0145">[9]</a>. Huang et al. reported that ROCK2 and MMP2 were markedly overexpressed in HCCs compared with that in the corresponding adjacent tissues, where a positive correlation in their expression was found. The knockdown of ROCK2 significantly decreased the expression of MMP2 and inhibited the invasion and metastasis of HCC in vitro and in vivo<a class="elsevierStyleCrossRef" href="#bib0195">[19]</a>. The MAGI2-AS3 and ROCK pathways both have crosstalk with Fas <a class="elsevierStyleCrossRefs" href="#bib0160">[12,13]</a>. Therefore, Fas may mediate the interaction between them. In addition, MAGI2-AS3 can function as the sponge of miRNAs, thus mediating the regulation of ROCK2 <a class="elsevierStyleCrossRef" href="#bib0170">[14]</a>. It was reported that ROCK2 could be suppressed by miR-130a in tumor tissues of HCC patients as well as four HCC cell lines, and resulted in inhibition of proliferation, migration and invasive ability of HCC cells <a class="elsevierStyleCrossRef" href="#bib0200">[20]</a>. It is also likely that MAGI2-AS3 may sponge a miRNA to regulate the expression of ROCK2. Our future studies will further explore this possibility.In conclusion, MAGI2-AS3 was downregulated in HCC and overexpression of MAGI2-AS3 inhibits cancer cell invasion and migration by downregulating ROCK2, thereby participating in distant recurrence of HCC. However, in vivo studies are needed to further verify our conclusions.DeclarationsPermission has been obtained for use of copyrighted material from other sources. Journal policies detailed in the guide have been reviewed.AbbreviationsHCChepatocellular carcinomaHBVHepatitis B virusHCVhepatitis C viruslncRNAslong (>200nt) non-coding RNAsConflict of interestThe authors declare that they have no conflict of interest.Ethical approvalThis study was approved by the ethics committee of affiliate hospital of Qingdao University. All procedures performed in participants were in accordance with the ethical standards of the Declaration of Helsinki. Informed consent was written by all participants." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1424246" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1301805" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Research subjects" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Plasma, treatment and a 3-year follow-up" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Cell lines and cell culture" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "RNA extractions and qPCR" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Cell migration and invasion analysis" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Western blot analysis" ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Statistical analysis" ] ] ] 4 => array:3 [ "identificador" => "sec0050" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "MAGI2-AS3 was downregulated in HCC and showed diagnostic values" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "The expression levels of MAGI2-AS3 were increased after resection of tumors and increased in HCC patients with distant recurrence during follow-up" ] 2 => array:2 [ "identificador" => "sec0065" "titulo" => "MAGI2-AS3 downregulated ROCK2 in HCC cells" ] 3 => array:2 [ "identificador" => "sec0070" "titulo" => "Overexpression of MAGI2-AS3 mediated the inhibition of HCC cell invasion, migration and apoptosis through ROCK2" ] ] ] 5 => array:2 [ "identificador" => "sec0075" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0080" "titulo" => "Declarations" ] 7 => array:2 [ "identificador" => "sec0085" "titulo" => "Abbreviations" ] 8 => array:2 [ "identificador" => "sec0090" "titulo" => "Conflict of interest" ] 9 => array:2 [ "identificador" => "sec0095" "titulo" => "Ethical approval" ] 10 => array:2 [ "identificador" => "xack497219" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-04-07" "fechaAceptado" => "2020-04-28" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1301805" "palabras" => array:4 [ 0 => "Hepatocellular carcinoma" 1 => "MAGI2-AS3" 2 => "Diagnosis" 3 => "ROCK2" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Introduction and objectivesHepatocellular carcinoma (HCC) is the second most lethal cancer around the world, with poor survival rate and high metastasis rate in patients. Long noncoding RNAs (lncRNAs) have been reported to modulate the initiation and development of liver cancer. We aimed to investigate the role of lncRNA MAGI2-AS3 in HCC and underlying mechanisms. Materials and methodsThe expression levels of MAGI2-AS3 in plasma of HCC patients and the control participants were measured by qPCR. Hep3B and MHCC97-H cells were transfected with MAGI2-AS3 and ROCK2 expression vectors. Cell migration and invasion of HCC cells transfected with the vectors were investigated by transwell assay. In addition, flow cytometry and western blot were performed for apoptosis detection. ResultsWe found that MAGI2-AS3 was downregulated in plasma of early stage HCC patients compared to healthy controls. After surgical resection, the expression levels of MAGI2-AS3 were increased compared to pretreatment levels on the day of discharge. During the follow-up, MAGI2-AS3 was downregulated in patients developed distant recurrence, but not in other patients compared to the levels measured on the day of discharge. In HCC cells, overexpression of MAGI2-AS3 mediated the downregulation of ROCK2. Cell invasion and migration assay showed that overexpression of MAGI2-AS3 mediated the decreased cell invasion and migration rate, while ROCK2 played an opposite role and attenuated the effects of overexpression of MAGI2-AS3. ConclusionOur study indicated that MAGI2-AS3 was downregulated in the distant recurrence of HCC after surgical resection and affected the invasion and migration of HCC cells via ROCK2." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1124 "Ancho" => 2667 "Tamanyo" => 225528 ] ] "descripcion" => array:1 [ "en" => "MAGI2-AS3 was downregulated in HCC patients and showed diagnostic values. Expression levels of MAGI2-AS3 in plasma of two groups of participants (HCC and Control) were measured by qPCR. Expression levels of MAGI2-AS3 were compared between 2 groups by performing unpaired test (A) (*, p<0.05). ROC curve was used to analyze the potentials of MAGI2-AS3 in the diagnosis of HCC. In ROC curve, true positive cases were HCC patients and true negative cases were healthy volunteers (B)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2377 "Ancho" => 2833 "Tamanyo" => 399550 ] ] "descripcion" => array:1 [ "en" => "Expression levels of MAGI2-AS3 were increased after resection of tumors and increased in HCC patients with distant recurrence during follow-up. Expression levels of MAGI2-AS3 in HCC patients were measured by qPCR at 3 time points – pre-treatment, discharge and follow-up. Plasma levels of MAGI2-AS3 were compared between pretreatment levels and the levels of the day of discharge (A). During follow-up, distance recurrence (combined with local recurrence in most cases) was observed in 27 cases, local recurrence (no distant recurrence) was observed in 22 cases, and the rest showed no recurrence. Comparisons of plasma levels of MAGI2-AS3 between discharge level and follow-up level were performed in patients with distant recurrence (B) patients with local recurrence (C) and patients with non-recurrence (D), (*, p<0.05)." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2297 "Ancho" => 3083 "Tamanyo" => 954842 ] ] "descripcion" => array:1 [ "en" => "MAGI2-AS3 downregulated ROCK2 in HCC cells. Hep3B and MHCC97-H cells were transfected with MAGI2-AS3 and ROCK2 expression vectors. Cell viability and transfection rates were shown (A). Overexpression of MAGI2-AS3 and ROCK2 were confirmed by qPCR (B). In addition, effects of MAGI2-AS3 on ROCK2 were analyzed by qPCR and western blot (C). Effects of overexpression of ROCK2 on the expression of MAGI2-AS3 were assessed by qPCR (D). Data were expressed as the mean±SD (n=3, *, p<0.05)." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 2159 "Ancho" => 3333 "Tamanyo" => 1028255 ] ] "descripcion" => array:1 [ "en" => "Overexpression of MAGI2-AS3 mediated the cell invasion, migration and apoptosis through ROCK2. Cell invasion and migration assays were performed to explore the effects of overexpression of MAGI2-AS3 and ROCK2 on invasion (A) and migration (B) of HCC cells. Apoptosis assays were performed by flow cytometry and caspase3 levels were measured by western blot (C). Data were expressed as the mean±SD (n=3, *, p<0.05)." ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Note: The mean expression level was used as the threshold. For analysis of association between MAGI2-AS3 levels and clinical features, Pearson's χ2 tests were used *p<0.05." "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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \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">Cases \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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MAGI2-AS3</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">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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">Low \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">High \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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 " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gender</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male \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">40 \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">22 \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">18 \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">0.321 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female \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">28 \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">14 \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">14 \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 " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (years)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>50 \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">39 \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">24 \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">15 \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">0.271 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><50 \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">29 \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">13 \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">16 \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 " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tumor size (cm)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥5cm \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">48 \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">29 \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">19 \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">0.023* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><5cm \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">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">13 \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">14 \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 " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Differentiation</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Low \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">33 \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">19 \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">14 \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">0.046* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High \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">35 \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">25 \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">10 \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 " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Metastasis</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NR \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">19 \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">7 \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">12 \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-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DR \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">27 \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">18 \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">9 \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">0.032* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LR \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">22 \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">13 \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">9 \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></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2442747.png" ] ] ] ] "descripcion" => array:1 [ "en" => "The correlation between the expression of lncRNA MAGI2-AS3 and clinicopathologic variables in patients with hepatocellular carcinoma." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0105" "etiqueta" => "[1]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cancer statistics, 2019" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.L. Siegel" 1 => "K.D. Miller" 2 => "A. Jemal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3322/caac.21551" "Revista" => array:7 [ "tituloSerie" => "CA Cancer J Clin" "fecha" => "2019" "volumen" => "69" "numero" => "1" "paginaInicial" => "7" "paginaFinal" => "34" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30620402" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0110" "etiqueta" => "[2]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global cancer statistics, 2002" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D.M. Parkin" 1 => "F. Bray" 2 => "J. Ferlay" 3 => "P. Pisani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3322/canjclin.55.2.74" "Revista" => array:7 [ "tituloSerie" => "CA Cancer J Clin" "fecha" => "2005" "volumen" => "55" "numero" => "2" "paginaInicial" => "74" "paginaFinal" => "108" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15761078" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0115" "etiqueta" => "[3]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatocellular carcinoma-cause, treatment and metastasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Z.Y. Tang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v7.i4.445" "Revista" => array:7 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2001" "volumen" => "7" "numero" => "4" "paginaInicial" => "445" "paginaFinal" => "454" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11819809" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0120" "etiqueta" => "[4]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The etiology of hepatocellular carcinoma and consequences for treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.J. Sanyal" 1 => "S.K. Yoon" 2 => "R. Lencioni" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1634/theoncologist.2010-S4-14" "Revista" => array:7 [ "tituloSerie" => "Oncologist" "fecha" => "2010" "volumen" => "15" "numero" => "Suppl. 4" "paginaInicial" => "14" "paginaFinal" => "22" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21115577" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0125" "etiqueta" => "[5]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Single HCC smaller than 2cm: surgery or ablation? Surgeon's perspective" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T. Takayama" 1 => "M. Makuuchi" 2 => "K. Hasegawa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00534-009-0239-7" "Revista" => array:7 [ "tituloSerie" => "J Hepatobiliary Pancreat Sci" "fecha" => "2010" "volumen" => "17" "numero" => "4" "paginaInicial" => "422" "paginaFinal" => "424" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19936598" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0130" "etiqueta" => "[6]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HCC: current surgical treatment concepts" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F. Cauchy" 1 => "D. Fuks" 2 => "J. Belghiti" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Langenbecks Arch Surg" "fecha" => "2012" "volumen" => "397" "numero" => "5" "paginaInicial" => "681" "paginaFinal" => "695" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0135" "etiqueta" => "[7]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Arzumanyan" 1 => "H.M. Reis" 2 => "M.A. Feitelson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrc3449" "Revista" => array:7 [ "tituloSerie" => "Nat Rev Cancer" "fecha" => "2013" "volumen" => "13" "numero" => "2" "paginaInicial" => "123" "paginaFinal" => "135" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23344543" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0140" "etiqueta" => "[8]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of viral hepatitis and hepatocellular carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "H.B. El-Serag" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2011.12.061" "Revista" => array:7 [ "tituloSerie" => "Gastroenterology" "fecha" => "2012" "volumen" => "142" "numero" => "6" "paginaInicial" => "1264" "paginaFinal" => "1273" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22537432" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0145" "etiqueta" => "[9]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rho-associated kinases in tumorigenesis: re-considering ROCK inhibition for cancer therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "N. Rath" 1 => "M.F. Olson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/embor.2012.127" "Revista" => array:7 [ "tituloSerie" => "EMBO Rep" "fecha" => "2012" "volumen" => "13" "numero" => "10" "paginaInicial" => "900" "paginaFinal" => "908" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22964758" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0150" "etiqueta" => "[10]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "LncRNAs regulate the cytoskeleton and related Rho/ROCK signaling in cancer metastasis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Tang" 1 => "Y. He" 2 => "P. Zhang" 3 => "J. Wang" 4 => "C. Fan" 5 => "L. Yang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12943-018-0825-x" "Revista" => array:6 [ "tituloSerie" => "Mol Cancer" "fecha" => "2018" "volumen" => "17" "numero" => "1" "paginaInicial" => "77" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29618386" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0155" "etiqueta" => "[11]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The hallmarks of cancer: a long non-coding RNA point of view" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T. Gutschner" 1 => "S. Diederichs" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4161/rna.20481" "Revista" => array:7 [ "tituloSerie" => "RNA Biol" "fecha" => "2012" "volumen" => "9" "numero" => "6" "paginaInicial" => "703" "paginaFinal" => "719" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22664915" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0160" "etiqueta" => "[12]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The cleaved FAS ligand activates the Na+/H+ exchanger NHE1 through Akt/ROCK1 to stimulate cell motility" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Monet" 1 => "M. Poët" 2 => "S. Tauzin" 3 => "A. Fouqué" 4 => "A. Cophignon" 5 => "D. Lagadic-Gossmann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/srep28008" "Revista" => array:5 [ "tituloSerie" => "Sci Rep" "fecha" => "2016" "volumen" => "6" "paginaInicial" => "28008" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27302366" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0165" "etiqueta" => "[13]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long non-coding RNA (lncRNA) MAGI2-AS3 inhibits breast cancer cell growth by targeting the Fas/FasL signalling pathway" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Yang" 1 => "H. Yang" 2 => "M. Xu" 3 => "H. Zhang" 4 => "M. Sun" 5 => "P. Mu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s13577-018-0206-1" "Revista" => array:7 [ "tituloSerie" => "Human Cell" "fecha" => "2018" "volumen" => "31" "numero" => "3" "paginaInicial" => "232" "paginaFinal" => "241" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29679339" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0170" "etiqueta" => "[14]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long noncoding RNA MAGI2-AS3 regulates CCDC19 expression by sponging miR-15b-5p and suppresses bladder cancer progression" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Wang" 1 => "Y. Zu" 2 => "S. Zhu" 3 => "Y. Yang" 4 => "W. Huang" 5 => "H. Xie" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbrc.2018.11.013" "Revista" => array:7 [ "tituloSerie" => "Biochem Biophys Res Commun" "fecha" => "2018" "volumen" => "507" "numero" => "1–4" "paginaInicial" => "231" "paginaFinal" => "235" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30442369" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0175" "etiqueta" => "[15]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of two different thermal techniques for the treatment of hepatocellular carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Ding" 1 => "X. Jing" 2 => "J. Liu" 3 => "Y. Wang" 4 => "F. Wang" 5 => "Y. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ejrad.2013.04.025" "Revista" => array:7 [ "tituloSerie" => "Eur J Radiol" "fecha" => "2013" "volumen" => "82" "numero" => "9" "paginaInicial" => "1379" "paginaFinal" => "1384" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23726122" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0180" "etiqueta" => "[16]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk factors for recurrence after transarterial chemoembolization for early-stage hepatocellular carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Kinugasa" 1 => "K. Nouso" 2 => "Y. Takeuchi" 3 => "T. asunaka" 4 => "H. Onishi" 5 => "S. Nakamura" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00535-011-0492-9" "Revista" => array:7 [ "tituloSerie" => "J Gastroenterol" "fecha" => "2012" "volumen" => "47" "numero" => "4" "paginaInicial" => "421" "paginaFinal" => "426" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22048256" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0185" "etiqueta" => "[17]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Surviving at a distance: organ-specific metastasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.C. Obenauf" 1 => "J. Massagué" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.trecan.2015.07.009" "Revista" => array:7 [ "tituloSerie" => "Trends Cancer" "fecha" => "2015" "volumen" => "1" "numero" => "1" "paginaInicial" => "76" "paginaFinal" => "91" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28741564" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0190" "etiqueta" => "[18]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "DLC-1 is an independent prognostic marker and potential therapeutic target in hepatocellular cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.J. Song" 1 => "Q. Liu" 2 => "X.R. Meng" 3 => "S.L. Li" 4 => "L.X. Wang" 5 => "Q.X. Fan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13000-016-0470-x" "Revista" => array:5 [ "tituloSerie" => "Diagn Pathol" "fecha" => "2016" "volumen" => "11" "paginaInicial" => "19" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26846339" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0195" "etiqueta" => "[19]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rock2 promotes the invasion and metastasis of hepatocellular carcinoma by modifying MMP2 ubiquitination and degradation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Huang" 1 => "X. Du" 2 => "R. Yuan" 3 => "L. Chen" 4 => "T. Liu" 5 => "C. Wen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbrc.2014.09.061" "Revista" => array:6 [ "tituloSerie" => "Biochem Biophys Res Commun" "fecha" => "2014" "volumen" => "453" "paginaInicial" => "49" "paginaFinal" => "56" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25251472" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0200" "etiqueta" => "[20]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "MicroRNA-130a inhibits the proliferation, migration and invasive ability of hepatocellular carcinoma cells by downregulating Rho-kinase 2" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Y. Zheng" 1 => "L. Xiang" 2 => "M. Chen" 3 => "C. Xiang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3892/mmr.2018.9283" "Revista" => array:6 [ "tituloSerie" => "Mol Med Rep" "fecha" => "2018" "volumen" => "18" "paginaInicial" => "3077" "paginaFinal" => "3084" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30015839" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack497219" "titulo" => "Acknowledgements" "texto" => "We thank for the financial support from the Microwave ablation in basic research of primary small hepatocellular carcinoma (40518040221)." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/0000001900000005/v5_202012011817/S1665268120300466/v5_202012011817/en/main.assets" "Apartado" => array:4 [ "identificador" => "78265" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/16652681/0000001900000005/v5_202012011817/S1665268120300466/v5_202012011817/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268120300466?idApp=UINPBA00004N"]

Statistics

Original article

Gang Fanga, Jianjun Wangb, Xiaowei Sunc, Rui Xud, Xiaolong Zhaod, Liming Shaod, Chengjing Sund, Yanhua Wangd,

Corresponding author

fbfjhr3398305@126.com

Corresponding author at:

a Department of Radiology, Jimo District Hospital of Traditional Chinese Medicine, Qingdao 266200, Shandong Province, China

b Department of Radiology, Traditional Chinese Medicine Medical Hospital of Zhucheng 262200, Shandong Province, China

c Qingdao Commercial Staff Hospital, Qingdao, Shandong Province, China

d The Interventional Medicine Center the Affiliated Hospital of Qingdao University China, Qingdao 266003, Shandong Province, China

Read

1211

Times
was read the article

384

Total PDF

827

Total HTML

Share statistics

 array:24 [
  "pii" => "S1665268120300466"
  "issn" => "16652681"
  "doi" => "10.1016/j.aohep.2020.04.007"
  "estado" => "S300"
  "fechaPublicacion" => "2020-09-01"
  "aid" => "205"
  "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
  "copyrightAnyo" => "2020"
  "documento" => "article"
  "crossmark" => 1
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "fla"
  "cita" => "Ann Hepatol. 2020;19:535-40"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemSiguiente" => array:18 [
    "pii" => "S1665268120300818"
    "issn" => "16652681"
    "doi" => "10.5604/01.3001.0012.2246"
    "estado" => "S300"
    "fechaPublicacion" => "2020-09-01"
    "aid" => "234"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Ann Hepatol. 2020;19:541-5"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Efficacy and safety of basiliximab as initial immunosuppression in liver transplantation&#58; A single center study"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "541"
          "paginaFinal" => "545"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0005"
          "etiqueta" => "Fig&#46; 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1261
              "Ancho" => 1583
              "Tamanyo" => 71064
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0005"
              "detalle" => "Fig&#46; "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Comparison of survival between both groups&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Mohamed Hashim, Ayman Alsebaey, Amr Ragab, Hossam Eldeen Soliman, Imam Waked"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "Mohamed"
              "apellidos" => "Hashim"
            ]
            1 => array:2 [
              "nombre" => "Ayman"
              "apellidos" => "Alsebaey"
            ]
            2 => array:2 [
              "nombre" => "Amr"
              "apellidos" => "Ragab"
            ]
            3 => array:2 [
              "nombre" => "Hossam Eldeen"
              "apellidos" => "Soliman"
            ]
            4 => array:2 [
              "nombre" => "Imam"
              "apellidos" => "Waked"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268120300818?idApp=UINPBA00004N"
    "url" => "/16652681/0000001900000005/v5_202012011817/S1665268120300818/v5_202012011817/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S1665268120300478"
    "issn" => "16652681"
    "doi" => "10.1016/j.aohep.2020.04.008"
    "estado" => "S300"
    "fechaPublicacion" => "2020-09-01"
    "aid" => "206"
    "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Ann Hepatol. 2020;19:530-4"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Propranolol for infantile hepatic hemangioendothelioma&#58; Clinical evaluation of drug efficacy and safety using a single-center patient cohort"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "530"
          "paginaFinal" => "534"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Fig&#46; 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1427
              "Ancho" => 3333
              "Tamanyo" => 256541
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Three-day-old female with IHHE diagnosed by enhanced MRI&#46; &#40;A&#44; B&#41; Magnetic Resonance Imaging revealing IHHE lesion before oral propranolol treatment&#46; &#40;C&#41; Ultrasound examination shows a lesion that decreased by about 100&#37; in volume&#44; after two months of oral propranolol treatment&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Ruicheng Tian, Yu Liang, Jing Wang, Yuhua Shan, Hongxiang Gao, Lei Zhang, Chenjie Xie, Jingjing Li, Min Xu, Song Gu"
          "autores" => array:10 [
            0 => array:2 [
              "nombre" => "Ruicheng"
              "apellidos" => "Tian"
            ]
            1 => array:2 [
              "nombre" => "Yu"
              "apellidos" => "Liang"
            ]
            2 => array:2 [
              "nombre" => "Jing"
              "apellidos" => "Wang"
            ]
            3 => array:2 [
              "nombre" => "Yuhua"
              "apellidos" => "Shan"
            ]
            4 => array:2 [
              "nombre" => "Hongxiang"
              "apellidos" => "Gao"
            ]
            5 => array:2 [
              "nombre" => "Lei"
              "apellidos" => "Zhang"
            ]
            6 => array:2 [
              "nombre" => "Chenjie"
              "apellidos" => "Xie"
            ]
            7 => array:2 [
              "nombre" => "Jingjing"
              "apellidos" => "Li"
            ]
            8 => array:2 [
              "nombre" => "Min"
              "apellidos" => "Xu"
            ]
            9 => array:2 [
              "nombre" => "Song"
              "apellidos" => "Gu"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268120300478?idApp=UINPBA00004N"
    "url" => "/16652681/0000001900000005/v5_202012011817/S1665268120300478/v5_202012011817/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "LncRNA MAGI2-AS3 is downregulated in the distant recurrence of hepatocellular carcinoma after surgical resection and affects migration and invasion via ROCK2"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "535"
        "paginaFinal" => "540"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Gang Fang, Jianjun Wang, Xiaowei Sun, Rui Xu, Xiaolong Zhao, Liming Shao, Chengjing Sun, Yanhua Wang"
        "autores" => array:8 [
          0 => array:3 [
            "nombre" => "Gang"
            "apellidos" => "Fang"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Jianjun"
            "apellidos" => "Wang"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Xiaowei"
            "apellidos" => "Sun"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Rui"
            "apellidos" => "Xu"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Xiaolong"
            "apellidos" => "Zhao"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Liming"
            "apellidos" => "Shao"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          6 => array:3 [
            "nombre" => "Chengjing"
            "apellidos" => "Sun"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          7 => array:4 [
            "nombre" => "Yanhua"
            "apellidos" => "Wang"
            "email" => array:1 [
              0 => "fbfjhr3398305@126.com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:4 [
          0 => array:3 [
            "entidad" => "Department of Radiology&#44; Jimo District Hospital of Traditional Chinese Medicine&#44; Qingdao 266200&#44; Shandong Province&#44; China"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Department of Radiology&#44; Traditional Chinese Medicine Medical Hospital of Zhucheng 262200&#44; Shandong Province&#44; China"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Qingdao Commercial Staff Hospital&#44; Qingdao&#44; Shandong Province&#44; China"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "The Interventional Medicine Center the Affiliated Hospital of Qingdao University China&#44; Qingdao 266003&#44; Shandong Province&#44; China"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author at&#58;"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2377
            "Ancho" => 2833
            "Tamanyo" => 399550
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Expression levels of MAGI2-AS3 were increased after resection of tumors and increased in HCC patients with distant recurrence during follow-up&#46; Expression levels of MAGI2-AS3 in HCC patients were measured by qPCR at 3 time points &#8211; pre-treatment&#44; discharge and follow-up&#46; Plasma levels of MAGI2-AS3 were compared between pretreatment levels and the levels of the day of discharge &#40;A&#41;&#46; During follow-up&#44; distance recurrence &#40;combined with local recurrence in most cases&#41; was observed in 27 cases&#44; local recurrence &#40;no distant recurrence&#41; was observed in 22 cases&#44; and the rest showed no recurrence&#46; Comparisons of plasma levels of MAGI2-AS3 between discharge level and follow-up level were performed in patients with distant recurrence &#40;B&#41; patients with local recurrence &#40;C&#41; and patients with non-recurrence &#40;D&#41;&#44; &#40;&#42;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">As the major subtype of liver cancer&#44; hepatocellular carcinoma &#40;HCC&#41; is the leading cause of cancer-related mortalities&#44; and its prevalence rate ranks the fifth place among all types of cancer <a class="elsevierStyleCrossRef" href="#bib0105">&#91;1&#93;</a>&#46; Even with the efforts that have been made on cancer prevention&#44; the incidence of HCC still showed an increasing trend in many countries&#44; such as China <a class="elsevierStyleCrossRef" href="#bib0110">&#91;2&#93;</a>&#46; At present&#44; effective therapeutic approaches for HCC patients at advanced stages are still lacking <a class="elsevierStyleCrossRefs" href="#bib0115">&#91;3&#44;4&#93;</a>&#46; Most HCC patients diagnosed at early stages are promising candidates for surgical resection&#44; which is the only radical therapy <a class="elsevierStyleCrossRef" href="#bib0125">&#91;5&#93;</a>&#46; Whereas&#44; recurrence with inevitably occurs in many cases&#44; leading to poor prognosis <a class="elsevierStyleCrossRef" href="#bib0130">&#91;6&#93;</a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Hepatitis B virus &#40;HBV&#41; and hepatitis C virus &#40;HCV&#41; infections are the major risk factors for HCC <a class="elsevierStyleCrossRefs" href="#bib0135">&#91;7&#44;8&#93;</a>&#46; However&#44; the infection itself is not sufficient to initiate HCC&#44; and multiple signaling pathways are also involved <a class="elsevierStyleCrossRefs" href="#bib0135">&#91;7&#44;8&#93;</a>&#46; Rho associated coiled-coil containing protein kinase 2 &#40;ROCK2&#41; is a critical regulator of actomyosin cytoskeleton and plays regulatory roles in motility and invasion of cancer cells <a class="elsevierStyleCrossRef" href="#bib0145">&#91;9&#93;</a>&#46; Inhibition of the expression of ROCK2 provides new insights into cancer treatment <a class="elsevierStyleCrossRef" href="#bib0145">&#91;9&#93;</a>&#46; ROCK2 can be regulated by certain long &#40;&#62;200<span class="elsevierStyleHsp" style=""></span>nt&#41; non-coding RNAs &#40;lncRNAs&#41; <a class="elsevierStyleCrossRef" href="#bib0150">&#91;10&#93;</a>&#44; which participate in cancer biology mainly through the regulation of gene expression <a class="elsevierStyleCrossRef" href="#bib0155">&#91;11&#93;</a>&#46; It is known that Fas may regulate the ROCK signaling <a class="elsevierStyleCrossRef" href="#bib0160">&#91;12&#93;</a>&#46; A recent study showed that a novel lncRNA MAGI2-AS3 regulated Fas to suppress breast cancer <a class="elsevierStyleCrossRef" href="#bib0165">&#91;13&#93;</a>&#46; Therefore&#44; MAGI2-AS3 may also have crosstalk with the ROCK signaling&#46; This study explored the interaction between MAGI2-AS3 and ROCK2 in HCC&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2</span><span class="elsevierStyleSectionTitle" id="sect0040">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0045">Research subjects</span><p id="par0015" class="elsevierStylePara elsevierViewall">The present study selected 68 HCC patients &#40;40 males and 28 females&#59; age range from 33 to 67 years old&#59; mean age 49&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;3 years old&#41; selected from 233 HCC patients admitted by the affiliate hospital of Qingdao University between April 2013 and January 2016&#46; Inclusion criteria&#58; &#40;1&#41; newly diagnosed HCC cases&#59; &#40;2&#41; no therapies were performed&#59; &#40;3&#41; early stage &#40;Stage1&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; stage 2&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>40&#41; HCC suitable for surgical resection&#46; Exclusion criteria&#58; &#40;1&#41; recurrent HCC&#59; &#40;2&#41; history of malignancies&#59; &#40;3&#41; with initiated therapies&#46; During the same time period&#44; 68 healthy volunteers &#40;40 males and 28 females&#59; age range from 34 to 68 years old&#59; mean age 49&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;0 years old&#41; were also enrolled&#46; All HCC patients and healthy volunteers signed the informed consent&#46; This study was approved by the Ethics Committee of aforementioned hospital&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;2</span><span class="elsevierStyleSectionTitle" id="sect0050">Plasma&#44; treatment and a 3-year follow-up</span><p id="par0020" class="elsevierStylePara elsevierViewall">Blood &#40;5<span class="elsevierStyleHsp" style=""></span>ml&#41; was extracted from each patient and healthy volunteer before any therapies&#46; Patients received surgical resection combined with different doses of chemotherapies and radiotherapies according to the conditions of the patients&#46; Blood &#40;5<span class="elsevierStyleHsp" style=""></span>ml&#41; was also extracted on the day of discharge&#46; After discharge&#44; all patients were followed-up for 3 years to record the recurrence&#46; During the follow-up&#44; same amount of blood was extract on the day of diagnosis of recurrence or at the end of follow-up &#40;in cases with no recurrence observed&#41;&#46; All blood samples were centrifuged in EDTA tubes at room temperature for 14<span class="elsevierStyleHsp" style=""></span>min to collect plasma &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;3</span><span class="elsevierStyleSectionTitle" id="sect0055">Cell lines and cell culture</span><p id="par0025" class="elsevierStylePara elsevierViewall">Hep3B and MHCC97-H &#40;ATCC&#44; USA&#41; cells were used&#44; which have high metastasis capacity&#46; Cells were cultivated in RPMI-1640 medium &#40;10&#37; FBS&#41; under the conditions of 5&#37; CO<span class="elsevierStyleInf">2</span> and 37<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; MAGI2-AS3 and ROCK2 expression vectors were established using pcDNA3&#46;1 vector &#40;RIBOBIO&#44; Guangzhou&#44; China&#41; as the backbone&#46; Hep3B and MHCC97-H cells were collected at confluence of 70&#8211;80&#37;&#44; and 10<span class="elsevierStyleSup">5</span> cells were transfected with 10<span class="elsevierStyleHsp" style=""></span>nM MAGI2-AS3 and ROCK2 expression vector or 10<span class="elsevierStyleHsp" style=""></span>nM pcDNA3&#46;1 &#40;negative control&#44; NC&#41; using lipofectamine 2000 &#40;Invitrogen&#44; USA&#41;&#46; The interval between cell transfection and subsequent experiment was 24<span class="elsevierStyleHsp" style=""></span>h&#46; Hep3B and MHCC97-H cells with no transfections were used as the Control &#40;C&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;4</span><span class="elsevierStyleSectionTitle" id="sect0060">RNA extractions and qPCR</span><p id="par0030" class="elsevierStylePara elsevierViewall">Trizol reagent &#40;Invitrogen&#44; USA&#41; was used to extract total RNAs&#46; In brief&#44; 0&#46;4<span class="elsevierStyleHsp" style=""></span>ml Trizol was mixed with 10<span class="elsevierStyleSup">5</span> H1993 or H1581 cells or 0&#46;1<span class="elsevierStyleHsp" style=""></span>ml plasma&#44; followed by centrifugation and ethanol participation&#46; All RNA samples were digested with DNase I&#44; followed by reverse transcription using the MMLV Reverse Transcriptase &#40;Lucigen&#44; USA&#41;&#46; All qPCR mixtures were prepared using the QuantiTect SYBR Green PCR Kit &#40;Qiagen&#44; Shanghai&#44; China&#41;&#46; The expression levels of MAGI2-AS3 and ROCK2 were determined with GAPDH as endogenous control&#46; The following primer sequences were used&#58; ROCK2 forward&#58; 5&#8242;-CTA GGCCGG GCG AAG-3 and reverse 5&#8242;-TCC AGC TTC CTC TGA CGAC-3&#8242;&#59; MAGI2-AS3 forward&#58; 5&#8242;-CACCTTGCTTGACAACTTGA-3&#8242; and reverse&#58; 5&#8242;-CATTACAGCTCGGCTACTGC-3&#8242;&#59; GAPDH forward&#58;5&#8242;-AAG GTG AAG GTC GGA GTCAA-3&#8242; and reverse&#58; 5&#8242;-AAT GAA GGG GTC ATT GAT GG-3&#46; All PCR reactions were prepared in triplicate manner and 2<span class="elsevierStyleSup">&#8722;&#916;&#916;CT</span> method was used to perform all data normalization&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;5</span><span class="elsevierStyleSectionTitle" id="sect0065">Cell migration and invasion analysis</span><p id="par0035" class="elsevierStylePara elsevierViewall">Hep3B and MHCC97-H cells were harvested and 3<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">4</span> cells were mixed with RPMI-1640 medium &#40;1&#37; FBS&#41; to prepare single cell suspensions&#46; Cells were transferred to Transwell upper chamber&#44; and each transfection group &#40;C&#44; NC&#44; overexpression&#41; included 3 replicated wells&#46; Before the invasion assay&#44; Matrigel &#40;356234&#44; Millipore&#44; USA&#41; was used to coat membrane to mimic <span class="elsevierStyleItalic">in vivo</span> invasion barrier&#46; Transwell lower chamber was added with RPMI-1640 medium &#40;20&#37; FBS&#41;&#46; Cells were cultivated for 12<span class="elsevierStyleHsp" style=""></span>h under the conditions of 5&#37; CO<span class="elsevierStyleInf">2</span> and 37<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; After staining using 1&#37; crystal violet &#40;Sigma&#8211;Aldrich&#44; USA&#41; at 22<span class="elsevierStyleHsp" style=""></span>&#176;C for 18<span class="elsevierStyleHsp" style=""></span>min&#44; a light microscope was used to count invading and migrating cells&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;6</span><span class="elsevierStyleSectionTitle" id="sect0070">Western blot analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Hep3B or MHCC97-H cells were harvested and counted&#44; and 10<span class="elsevierStyleSup">5</span> cells were mixed with 0&#46;6<span class="elsevierStyleHsp" style=""></span>ml RIPA solution &#40;RIBOBIO&#44; Guangzhou&#44; China&#41; to extract total proteins&#46; Protein samples were quantified and denatured in boiled water for 6<span class="elsevierStyleHsp" style=""></span>min&#44; followed by electrophoresis using 12&#37; SDS-PAGE gel&#46; Gel transfer &#40;PVDF membrane&#41; and blocking &#40;2<span class="elsevierStyleHsp" style=""></span>h in 5&#37; non-fate milk&#41; were then performed&#44; followed by incubation with primary antibodies of rabbit polyclonal ROCK2 &#40;1&#58;900&#44; ab71598&#44; Abcam&#41;&#44; Caspase 3&#40;1&#58;900&#44; ab13847&#44; Abcam&#41; and GAPDH antibody &#40;1&#58; 900&#44; ab37168&#44; Abcam&#41; at 4<span class="elsevierStyleHsp" style=""></span>&#176;C for 12<span class="elsevierStyleHsp" style=""></span>h&#46; After that&#44; membranes were further incubated with Goat anti-Rabbit IgG &#40;H<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>L&#41; HRP secondary antibody &#40;Thermo Fisher Scientific&#44; Inc&#41; at 22<span class="elsevierStyleHsp" style=""></span>&#176;C for 2<span class="elsevierStyleHsp" style=""></span>h&#46; ECL &#40;Sigma&#8211;Aldrich&#44; USA&#41; was used to develop signals&#46; Gray values were normalized using the Image J v1&#46;46 software&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;7</span><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">All data analyses were performed using the mean values of 3 biological replicates&#46; Differences between two groups &#40;HCC <span class="elsevierStyleItalic">vs&#46;</span> Control&#41; were explored using unpaired t test&#46; Differences among different cell transfection groups were explored by ANOVA &#40;one-way&#41; and Tukey test&#46; ROC curve was used to analyze the potentials of MAGI2-AS3 in the diagnosis of HCC&#46; In ROC curve&#44; true positive cases were HCC patients and true negative cases were healthy volunteers&#46; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered as statistically significant&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3</span><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0085">MAGI2-AS3 was downregulated in HCC and showed diagnostic values</span><p id="par0050" class="elsevierStylePara elsevierViewall">The levels of MAGI2-AS3 in plasma of two groups of participants &#40;HCC patients and the Control&#41; were measured by qPCR&#46; The results showed that the expression levels of MAGI2-AS3 were significantly lower in HCC patients compared to that in the Control group &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; ROC curve was used to analyze the potentials of MAGI2-AS3 in the diagnosis of HCC&#46; In ROC curve&#44; true positive cases were HCC patients and true negative cases were healthy volunteers&#46; As shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#44; the area under the curve was 0&#46;9138&#44; with 95&#37; confidence interval of 0&#46;8701&#8211;0&#46;9575 and a standard error of 0&#46;02231&#44; which indicated that the diagnosis model was reliable&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;2</span><span class="elsevierStyleSectionTitle" id="sect0090">The expression levels of MAGI2-AS3 were increased after resection of tumors and increased in HCC patients with distant recurrence during follow-up</span><p id="par0055" class="elsevierStylePara elsevierViewall">The expression levels of MAGI2-AS3 in plasma of HCC patients were measured by qPCR at 3 time points&#44; including pre-treatment&#44; discharge and the follow-up&#46; Compared to pretreatment&#44; the expression levels of MAGI2-AS3 were increased on the day of discharge &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; During follow-up&#44; distance recurrence &#40;combined with local recurrence in most cases&#41; was observed in 27 cases&#44; local recurrence &#40;no distant recurrence&#41; was observed in 22 cases&#44; and the rest showed no recurrence&#46; The expression levels of MAGI2-AS3 were significantly downregulated in patients with distant recurrence compared to that on the day of discharge &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; but not in patients with local recurrence &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>C&#41; or non-recurrence &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>D&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;3</span><span class="elsevierStyleSectionTitle" id="sect0095">MAGI2-AS3 downregulated ROCK2 in HCC cells</span><p id="par0060" class="elsevierStylePara elsevierViewall">Hep3B and MHCC97-H cells were transfected with MAGI2-AS3 and ROCK2 expression vectors&#44; with their cell viability and transfection rate shown in <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>A&#46; Compared to C and NC controls&#44; the expression levels of MAGI2-AS3 and ROCK2 were significantly increased at 24<span class="elsevierStyleHsp" style=""></span>h post-transfections &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>B&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; In addition&#44; overexpression of MAGI2-AS3 mediated the downregulation of ROCK2 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>C&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; at both RNA and protein levels&#44; while the expression of MAGI2-AS3 was not affected by overexpression of ROCK2 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>D&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;4</span><span class="elsevierStyleSectionTitle" id="sect0100">Overexpression of MAGI2-AS3 mediated the inhibition of HCC cell invasion&#44; migration and apoptosis through ROCK2</span><p id="par0065" class="elsevierStylePara elsevierViewall">Cell invasion and migration assay showed that&#44; compared to C and NC groups&#44; overexpression of MAGI2-AS3 led to decreased cell invasion &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>A&#41; and migration &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>B&#41; rate in Hep3B and MHCC-97H cells&#44; while ROCK2 played an opposite role and attenuated the effects of overexpression of MAGI2-AS3 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; Flow cytometry demonstrated that overexpression of MAGI2-AS3 could induce HCC cell death while the effects were attenuated by the overexpression of ROCK2&#46; In consistent with the apoptosis results&#44; caspase3 splicing was activated by MAGI2-AS3 due to the decreased expression levels of total caspase3&#44; while ROCK2 played the opposite role &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>C&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">4</span><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">In this study we detected the expression of MAGI2-AS3 in HCC&#46; We found that MAGI2-AS3 was downregulated in HCC patients and might participate in distant recurrence of HCC after surgery by regulating invasion and migration of cancer cells through the interactions with ROCK2&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">MAGI2-AS3 was closely related to cell proliferation&#44; invasion and migration in breast cancer and bladder cancer <a class="elsevierStyleCrossRefs" href="#bib0165">&#91;13&#44;14&#93;</a>&#46; In breast cancer&#44; MAGI2-AS3 suppresses cancer cell proliferation and induces cancer cell apoptosis by activating the Fas&#47;FasL signaling pathway <a class="elsevierStyleCrossRef" href="#bib0165">&#91;13&#93;</a>&#46; In bladder cancer&#44; MAGI2-AS3 sponges miR-15b-5p to upregulate tumor suppressive CCDC19&#44; thereby inhibiting the growth of cancer cell <a class="elsevierStyleCrossRef" href="#bib0170">&#91;14&#93;</a>&#46; In our study&#44; we observed the downregulation of MAGI2-AS3 in HCC&#46; In addition&#44; inhibited invasion and migration of cancer cells were observed after the overexpression of MAGI2-AS3&#46; Thus&#44; MAGI2-AS3 also played a tumor suppressive role in HCC&#44; which is consistent with previous studies&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Compared to local recurrence&#44; distant cancer recurrence is more aggressive <a class="elsevierStyleCrossRefs" href="#bib0175">&#91;15&#44;16&#93;</a>&#46; A recent study showed that the total recurrence rate of HCC patients after chemoembolization within 1 year is 68&#46;5&#37; <a class="elsevierStyleCrossRef" href="#bib0180">&#91;16&#93;</a>&#44; and a considerable portion of recurrent HCC patients developed distant recurrence&#46; Among the 68 patients included in this study&#44; 49 of them &#40;72&#46;1&#37;&#41; developed recurrence within 3 years after discharge&#46; We observed that MAGI2-AS3 was upregulated after surgical resection and downregulated after distant recurrence but not local recurrence&#46; Therefore&#44; monitoring the expression of MAGI2-AS3 may provide insights into the prediction of treatment outcomes of HCC after surgery&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Cancer cell invasion and migration play pivotal roles in cancer distant recurrence <a class="elsevierStyleCrossRef" href="#bib0185">&#91;17&#93;</a>&#46; In the present study&#44; we showed that MAGI2-AS3 in HCC cells can inhibit the expression of ROCK2&#44; which is highly expressed in HCC tissues <a class="elsevierStyleCrossRef" href="#bib0190">&#91;18&#93;</a> and promotes cancer cell motility and invasion <a class="elsevierStyleCrossRef" href="#bib0145">&#91;9&#93;</a>&#46; Huang et al&#46; reported that ROCK2 and MMP2 were markedly overexpressed in HCCs compared with that in the corresponding adjacent tissues&#44; where a positive correlation in their expression was found&#46; The knockdown of ROCK2 significantly decreased the expression of MMP2 and inhibited the invasion and metastasis of HCC <span class="elsevierStyleItalic">in vitro</span> and <span class="elsevierStyleItalic">in vivo</span><a class="elsevierStyleCrossRef" href="#bib0195">&#91;19&#93;</a>&#46; The MAGI2-AS3 and ROCK pathways both have crosstalk with Fas <a class="elsevierStyleCrossRefs" href="#bib0160">&#91;12&#44;13&#93;</a>&#46; Therefore&#44; Fas may mediate the interaction between them&#46; In addition&#44; MAGI2-AS3 can function as the sponge of miRNAs&#44; thus mediating the regulation of ROCK2 <a class="elsevierStyleCrossRef" href="#bib0170">&#91;14&#93;</a>&#46; It was reported that ROCK2 could be suppressed by miR-130a in tumor tissues of HCC patients as well as four HCC cell lines&#44; and resulted in inhibition of proliferation&#44; migration and invasive ability of HCC cells <a class="elsevierStyleCrossRef" href="#bib0200">&#91;20&#93;</a>&#46; It is also likely that MAGI2-AS3 may sponge a miRNA to regulate the expression of ROCK2&#46; Our future studies will further explore this possibility&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">In conclusion&#44; MAGI2-AS3 was downregulated in HCC and overexpression of MAGI2-AS3 inhibits cancer cell invasion and migration by downregulating ROCK2&#44; thereby participating in distant recurrence of HCC&#46; However&#44; <span class="elsevierStyleItalic">in vivo</span> studies are needed to further verify our conclusions&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Declarations</span><p id="par0095" class="elsevierStylePara elsevierViewall">Permission has been obtained for use of copyrighted material from other sources&#46; Journal policies detailed in the guide have been reviewed&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Abbreviations</span><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleDefList"><span class="elsevierStyleDefTerm">HCC</span><span class="elsevierStyleDefDescription"><p id="par0105" class="elsevierStylePara elsevierViewall">hepatocellular carcinoma</p></span><span class="elsevierStyleDefTerm">HBV</span><span class="elsevierStyleDefDescription"><p id="par0110" class="elsevierStylePara elsevierViewall">Hepatitis B virus</p></span><span class="elsevierStyleDefTerm">HCV</span><span class="elsevierStyleDefDescription"><p id="par0115" class="elsevierStylePara elsevierViewall">hepatitis C virus</p></span><span class="elsevierStyleDefTerm">lncRNAs</span><span class="elsevierStyleDefDescription"><p id="par0120" class="elsevierStylePara elsevierViewall">long &#40;&#62;200<span class="elsevierStyleHsp" style=""></span>nt&#41; non-coding RNAs</p></span></span></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Ethical approval</span><p id="par0130" class="elsevierStylePara elsevierViewall">This study was approved by the ethics committee of affiliate hospital of Qingdao University&#46; All procedures performed in participants were in accordance with the ethical standards of the Declaration of Helsinki&#46; Informed consent was written by all participants&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:12 [
        0 => array:3 [
          "identificador" => "xres1424246"
          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Introduction and objectives"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Materials and methods"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Results"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Conclusion"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1301805"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        3 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Materials and methods"
          "secciones" => array:7 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Research subjects"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Plasma&#44; treatment and a 3-year follow-up"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Cell lines and cell culture"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "RNA extractions and qPCR"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Cell migration and invasion analysis"
            ]
            5 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Western blot analysis"
            ]
            6 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        4 => array:3 [
          "identificador" => "sec0050"
          "titulo" => "Results"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "MAGI2-AS3 was downregulated in HCC and showed diagnostic values"
            ]
            1 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "The expression levels of MAGI2-AS3 were increased after resection of tumors and increased in HCC patients with distant recurrence during follow-up"
            ]
            2 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "MAGI2-AS3 downregulated ROCK2 in HCC cells"
            ]
            3 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Overexpression of MAGI2-AS3 mediated the inhibition of HCC cell invasion&#44; migration and apoptosis through ROCK2"
            ]
          ]
        ]
        5 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Discussion"
        ]
        6 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Declarations"
        ]
        7 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Abbreviations"
        ]
        8 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Conflict of interest"
        ]
        9 => array:2 [
          "identificador" => "sec0095"
          "titulo" => "Ethical approval"
        ]
        10 => array:2 [
          "identificador" => "xack497219"
          "titulo" => "Acknowledgements"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-04-07"
    "fechaAceptado" => "2020-04-28"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1301805"
          "palabras" => array:4 [
            0 => "Hepatocellular carcinoma"
            1 => "MAGI2-AS3"
            2 => "Diagnosis"
            3 => "ROCK2"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hepatocellular carcinoma &#40;HCC&#41; is the second most lethal cancer around the world&#44; with poor survival rate and high metastasis rate in patients&#46; Long noncoding RNAs &#40;lncRNAs&#41; have been reported to modulate the initiation and development of liver cancer&#46; We aimed to investigate the role of lncRNA MAGI2-AS3 in HCC and underlying mechanisms&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The expression levels of MAGI2-AS3 in plasma of HCC patients and the control participants were measured by qPCR&#46; Hep3B and MHCC97-H cells were transfected with MAGI2-AS3 and ROCK2 expression vectors&#46; Cell migration and invasion of HCC cells transfected with the vectors were investigated by transwell assay&#46; In addition&#44; flow cytometry and western blot were performed for apoptosis detection&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We found that MAGI2-AS3 was downregulated in plasma of early stage HCC patients compared to healthy controls&#46; After surgical resection&#44; the expression levels of MAGI2-AS3 were increased compared to pretreatment levels on the day of discharge&#46; During the follow-up&#44; MAGI2-AS3 was downregulated in patients developed distant recurrence&#44; but not in other patients compared to the levels measured on the day of discharge&#46; In HCC cells&#44; overexpression of MAGI2-AS3 mediated the downregulation of ROCK2&#46; Cell invasion and migration assay showed that overexpression of MAGI2-AS3 mediated the decreased cell invasion and migration rate&#44; while ROCK2 played an opposite role and attenuated the effects of overexpression of MAGI2-AS3&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Our study indicated that MAGI2-AS3 was downregulated in the distant recurrence of HCC after surgical resection and affected the invasion and migration of HCC cells via ROCK2&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction and objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Materials and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
          ]
        ]
      ]
    ]
    "multimedia" => array:5 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1124
            "Ancho" => 2667
            "Tamanyo" => 225528
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">MAGI2-AS3 was downregulated in HCC patients and showed diagnostic values&#46; Expression levels of MAGI2-AS3 in plasma of two groups of participants &#40;HCC and Control&#41; were measured by qPCR&#46; Expression levels of MAGI2-AS3 were compared between 2 groups by performing unpaired test &#40;A&#41; &#40;&#42;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; ROC curve was used to analyze the potentials of MAGI2-AS3 in the diagnosis of HCC&#46; In ROC curve&#44; true positive cases were HCC patients and true negative cases were healthy volunteers &#40;B&#41;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2377
            "Ancho" => 2833
            "Tamanyo" => 399550
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Expression levels of MAGI2-AS3 were increased after resection of tumors and increased in HCC patients with distant recurrence during follow-up&#46; Expression levels of MAGI2-AS3 in HCC patients were measured by qPCR at 3 time points &#8211; pre-treatment&#44; discharge and follow-up&#46; Plasma levels of MAGI2-AS3 were compared between pretreatment levels and the levels of the day of discharge &#40;A&#41;&#46; During follow-up&#44; distance recurrence &#40;combined with local recurrence in most cases&#41; was observed in 27 cases&#44; local recurrence &#40;no distant recurrence&#41; was observed in 22 cases&#44; and the rest showed no recurrence&#46; Comparisons of plasma levels of MAGI2-AS3 between discharge level and follow-up level were performed in patients with distant recurrence &#40;B&#41; patients with local recurrence &#40;C&#41; and patients with non-recurrence &#40;D&#41;&#44; &#40;&#42;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 2297
            "Ancho" => 3083
            "Tamanyo" => 954842
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">MAGI2-AS3 downregulated ROCK2 in HCC cells&#46; Hep3B and MHCC97-H cells were transfected with MAGI2-AS3 and ROCK2 expression vectors&#46; Cell viability and transfection rates were shown &#40;A&#41;&#46; Overexpression of MAGI2-AS3 and ROCK2 were confirmed by qPCR &#40;B&#41;&#46; In addition&#44; effects of MAGI2-AS3 on ROCK2 were analyzed by qPCR and western blot &#40;C&#41;&#46; Effects of overexpression of ROCK2 on the expression of MAGI2-AS3 were assessed by qPCR &#40;D&#41;&#46; Data were expressed as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#44; &#42;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 2159
            "Ancho" => 3333
            "Tamanyo" => 1028255
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Overexpression of MAGI2-AS3 mediated the cell invasion&#44; migration and apoptosis through ROCK2&#46; Cell invasion and migration assays were performed to explore the effects of overexpression of MAGI2-AS3 and ROCK2 on invasion &#40;A&#41; and migration &#40;B&#41; of HCC cells&#46; Apoptosis assays were performed by flow cytometry and caspase3 levels were measured by western blot &#40;C&#41;&#46; Data were expressed as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#44; &#42;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Note</span>&#58; The mean expression level was used as the threshold&#46; For analysis of association between MAGI2-AS3 levels and clinical features&#44; Pearson&#39;s <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> tests were used &#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p>"
          "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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&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">Cases&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  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MAGI2-AS3</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"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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">Low&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">High&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gender</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male&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">40&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">22&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">18&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">0&#46;321&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female&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">28&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">14&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">14&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  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;years&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62;50&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">39&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">24&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">15&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">0&#46;271&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;50&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">29&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">13&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">16&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  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tumor size &#40;cm&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805;5<span class="elsevierStyleHsp" style=""></span>cm&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">48&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">29&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">19&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">0&#46;023&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;5<span class="elsevierStyleHsp" style=""></span>cm&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">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">13&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">14&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  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Differentiation</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Low&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">33&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">19&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">14&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">0&#46;046&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>High&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">35&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">25&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">10&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  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Metastasis</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>NR&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">19&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">7&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">12&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-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DR&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">27&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">18&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">9&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">0&#46;032&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>LR&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">22&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">13&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">9&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></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2442747.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The correlation between the expression of lncRNA MAGI2-AS3 and clinicopathologic variables in patients with hepatocellular carcinoma&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:20 [
            0 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "&#91;1&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cancer statistics&#44; 2019"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46;L&#46; Siegel"
                            1 => "K&#46;D&#46; Miller"
                            2 => "A&#46; Jemal"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3322/caac.21551"
                      "Revista" => array:7 [
                        "tituloSerie" => "CA Cancer J Clin"
                        "fecha" => "2019"
                        "volumen" => "69"
                        "numero" => "1"
                        "paginaInicial" => "7"
                        "paginaFinal" => "34"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30620402"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "&#91;2&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global cancer statistics&#44; 2002"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46;M&#46; Parkin"
                            1 => "F&#46; Bray"
                            2 => "J&#46; Ferlay"
                            3 => "P&#46; Pisani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3322/canjclin.55.2.74"
                      "Revista" => array:7 [
                        "tituloSerie" => "CA Cancer J Clin"
                        "fecha" => "2005"
                        "volumen" => "55"
                        "numero" => "2"
                        "paginaInicial" => "74"
                        "paginaFinal" => "108"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15761078"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "&#91;3&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatocellular carcinoma-cause&#44; treatment and metastasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Z&#46;Y&#46; Tang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3748/wjg.v7.i4.445"
                      "Revista" => array:7 [
                        "tituloSerie" => "World J Gastroenterol"
                        "fecha" => "2001"
                        "volumen" => "7"
                        "numero" => "4"
                        "paginaInicial" => "445"
                        "paginaFinal" => "454"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11819809"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "&#91;4&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The etiology of hepatocellular carcinoma and consequences for treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;J&#46; Sanyal"
                            1 => "S&#46;K&#46; Yoon"
                            2 => "R&#46; Lencioni"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1634/theoncologist.2010-S4-14"
                      "Revista" => array:7 [
                        "tituloSerie" => "Oncologist"
                        "fecha" => "2010"
                        "volumen" => "15"
                        "numero" => "Suppl&#46; 4"
                        "paginaInicial" => "14"
                        "paginaFinal" => "22"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21115577"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "&#91;5&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Single HCC smaller than 2<span class="elsevierStyleHsp" style=""></span>cm&#58; surgery or ablation&#63; Surgeon&#39;s perspective"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "T&#46; Takayama"
                            1 => "M&#46; Makuuchi"
                            2 => "K&#46; Hasegawa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00534-009-0239-7"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Hepatobiliary Pancreat Sci"
                        "fecha" => "2010"
                        "volumen" => "17"
                        "numero" => "4"
                        "paginaInicial" => "422"
                        "paginaFinal" => "424"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19936598"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "&#91;6&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "HCC&#58; current surgical treatment concepts"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "F&#46; Cauchy"
                            1 => "D&#46; Fuks"
                            2 => "J&#46; Belghiti"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Langenbecks Arch Surg"
                        "fecha" => "2012"
                        "volumen" => "397"
                        "numero" => "5"
                        "paginaInicial" => "681"
                        "paginaFinal" => "695"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "&#91;7&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Arzumanyan"
                            1 => "H&#46;M&#46; Reis"
                            2 => "M&#46;A&#46; Feitelson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrc3449"
                      "Revista" => array:7 [
                        "tituloSerie" => "Nat Rev Cancer"
                        "fecha" => "2013"
                        "volumen" => "13"
                        "numero" => "2"
                        "paginaInicial" => "123"
                        "paginaFinal" => "135"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23344543"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "&#91;8&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of viral hepatitis and hepatocellular carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "H&#46;B&#46; El-Serag"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2011.12.061"
                      "Revista" => array:7 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2012"
                        "volumen" => "142"
                        "numero" => "6"
                        "paginaInicial" => "1264"
                        "paginaFinal" => "1273"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22537432"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "&#91;9&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rho-associated kinases in tumorigenesis&#58; re-considering ROCK inhibition for cancer therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "N&#46; Rath"
                            1 => "M&#46;F&#46; Olson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/embor.2012.127"
                      "Revista" => array:7 [
                        "tituloSerie" => "EMBO Rep"
                        "fecha" => "2012"
                        "volumen" => "13"
                        "numero" => "10"
                        "paginaInicial" => "900"
                        "paginaFinal" => "908"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22964758"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "&#91;10&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "LncRNAs regulate the cytoskeleton and related Rho&#47;ROCK signaling in cancer metastasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Tang"
                            1 => "Y&#46; He"
                            2 => "P&#46; Zhang"
                            3 => "J&#46; Wang"
                            4 => "C&#46; Fan"
                            5 => "L&#46; Yang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s12943-018-0825-x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Cancer"
                        "fecha" => "2018"
                        "volumen" => "17"
                        "numero" => "1"
                        "paginaInicial" => "77"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29618386"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "&#91;11&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The hallmarks of cancer&#58; a long non-coding RNA point of view"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "T&#46; Gutschner"
                            1 => "S&#46; Diederichs"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.4161/rna.20481"
                      "Revista" => array:7 [
                        "tituloSerie" => "RNA Biol"
                        "fecha" => "2012"
                        "volumen" => "9"
                        "numero" => "6"
                        "paginaInicial" => "703"
                        "paginaFinal" => "719"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22664915"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "&#91;12&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The cleaved FAS ligand activates the Na&#43;&#47;H&#43; exchanger NHE1 through Akt&#47;ROCK1 to stimulate cell motility"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Monet"
                            1 => "M&#46; Po&#235;t"
                            2 => "S&#46; Tauzin"
                            3 => "A&#46; Fouqu&#233;"
                            4 => "A&#46; Cophignon"
                            5 => "D&#46; Lagadic-Gossmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/srep28008"
                      "Revista" => array:5 [
                        "tituloSerie" => "Sci Rep"
                        "fecha" => "2016"
                        "volumen" => "6"
                        "paginaInicial" => "28008"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27302366"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "&#91;13&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long non-coding RNA &#40;lncRNA&#41; MAGI2-AS3 inhibits breast cancer cell growth by targeting the Fas&#47;FasL signalling pathway"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Yang"
                            1 => "H&#46; Yang"
                            2 => "M&#46; Xu"
                            3 => "H&#46; Zhang"
                            4 => "M&#46; Sun"
                            5 => "P&#46; Mu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s13577-018-0206-1"
                      "Revista" => array:7 [
                        "tituloSerie" => "Human Cell"
                        "fecha" => "2018"
                        "volumen" => "31"
                        "numero" => "3"
                        "paginaInicial" => "232"
                        "paginaFinal" => "241"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29679339"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "&#91;14&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long noncoding RNA MAGI2-AS3 regulates CCDC19 expression by sponging miR-15b-5p and suppresses bladder cancer progression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Wang"
                            1 => "Y&#46; Zu"
                            2 => "S&#46; Zhu"
                            3 => "Y&#46; Yang"
                            4 => "W&#46; Huang"
                            5 => "H&#46; Xie"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbrc.2018.11.013"
                      "Revista" => array:7 [
                        "tituloSerie" => "Biochem Biophys Res Commun"
                        "fecha" => "2018"
                        "volumen" => "507"
                        "numero" => "1&#8211;4"
                        "paginaInicial" => "231"
                        "paginaFinal" => "235"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30442369"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "&#91;15&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of two different thermal techniques for the treatment of hepatocellular carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Ding"
                            1 => "X&#46; Jing"
                            2 => "J&#46; Liu"
                            3 => "Y&#46; Wang"
                            4 => "F&#46; Wang"
                            5 => "Y&#46; Wang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ejrad.2013.04.025"
                      "Revista" => array:7 [
                        "tituloSerie" => "Eur J Radiol"
                        "fecha" => "2013"
                        "volumen" => "82"
                        "numero" => "9"
                        "paginaInicial" => "1379"
                        "paginaFinal" => "1384"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23726122"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "&#91;16&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk factors for recurrence after transarterial chemoembolization for early-stage hepatocellular carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Kinugasa"
                            1 => "K&#46; Nouso"
                            2 => "Y&#46; Takeuchi"
                            3 => "T&#46; asunaka"
                            4 => "H&#46; Onishi"
                            5 => "S&#46; Nakamura"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00535-011-0492-9"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Gastroenterol"
                        "fecha" => "2012"
                        "volumen" => "47"
                        "numero" => "4"
                        "paginaInicial" => "421"
                        "paginaFinal" => "426"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22048256"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "&#91;17&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Surviving at a distance&#58; organ-specific metastasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;C&#46; Obenauf"
                            1 => "J&#46; Massagu&#233;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.trecan.2015.07.009"
                      "Revista" => array:7 [
                        "tituloSerie" => "Trends Cancer"
                        "fecha" => "2015"
                        "volumen" => "1"
                        "numero" => "1"
                        "paginaInicial" => "76"
                        "paginaFinal" => "91"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28741564"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "&#91;18&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "DLC-1 is an independent prognostic marker and potential therapeutic target in hepatocellular cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;J&#46; Song"
                            1 => "Q&#46; Liu"
                            2 => "X&#46;R&#46; Meng"
                            3 => "S&#46;L&#46; Li"
                            4 => "L&#46;X&#46; Wang"
                            5 => "Q&#46;X&#46; Fan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13000-016-0470-x"
                      "Revista" => array:5 [
                        "tituloSerie" => "Diagn Pathol"
                        "fecha" => "2016"
                        "volumen" => "11"
                        "paginaInicial" => "19"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26846339"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "&#91;19&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rock2 promotes the invasion and metastasis of hepatocellular carcinoma by modifying MMP2 ubiquitination and degradation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Huang"
                            1 => "X&#46; Du"
                            2 => "R&#46; Yuan"
                            3 => "L&#46; Chen"
                            4 => "T&#46; Liu"
                            5 => "C&#46; Wen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbrc.2014.09.061"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biochem Biophys Res Commun"
                        "fecha" => "2014"
                        "volumen" => "453"
                        "paginaInicial" => "49"
                        "paginaFinal" => "56"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25251472"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "&#91;20&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "MicroRNA-130a inhibits the proliferation&#44; migration and invasive ability of hepatocellular carcinoma cells by downregulating Rho-kinase 2"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Y&#46; Zheng"
                            1 => "L&#46; Xiang"
                            2 => "M&#46; Chen"
                            3 => "C&#46; Xiang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3892/mmr.2018.9283"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Med Rep"
                        "fecha" => "2018"
                        "volumen" => "18"
                        "paginaInicial" => "3077"
                        "paginaFinal" => "3084"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30015839"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack497219"
        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0135" class="elsevierStylePara elsevierViewall">We thank for the financial support from the Microwave ablation in basic research of primary small hepatocellular carcinoma &#40;40518040221&#41;&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/16652681/0000001900000005/v5_202012011817/S1665268120300466/v5_202012011817/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "78265"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original Articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/16652681/0000001900000005/v5_202012011817/S1665268120300466/v5_202012011817/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268120300466?idApp=UINPBA00004N"
]

Article information

ISSN: 16652681
Original language: English

DOI:10.1016/j.aohep.2020.04.007

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	6	0	6
2024 October	7	3	10
2024 September	15	5	20
2024 August	13	6	19
2024 July	8	4	12
2024 June	9	3	12
2024 May	8	2	10
2024 April	11	16	27
2024 March	19	8	27
2024 February	11	4	15
2024 January	10	6	16
2023 December	11	3	14
2023 November	10	8	18
2023 October	14	9	23
2023 September	9	1	10
2023 August	7	2	9
2023 July	14	2	16
2023 June	24	6	30
2023 May	50	3	53
2023 April	32	1	33
2023 March	10	1	11
2023 February	9	8	17
2023 January	13	4	17
2022 December	18	9	27
2022 November	23	7	30
2022 October	20	7	27
2022 September	22	21	43
2022 August	14	13	27
2022 July	85	6	91
2022 June	7	6	13
2022 May	12	12	24
2022 April	7	8	15
2022 March	15	4	19
2022 February	13	3	16
2022 January	24	7	31
2021 December	15	11	26
2021 November	9	6	15
2021 October	12	6	18
2021 September	11	11	22
2021 August	8	6	14
2021 July	9	6	15
2021 June	9	12	21
2021 May	10	9	19
2021 April	23	12	35
2021 March	32	8	40
2021 February	7	10	17
2021 January	9	13	22
2020 December	11	10	21
2020 November	13	7	20
2020 October	13	8	21
2020 September	35	10	45
2020 August	9	16	25
2020 July	6	5	11
2020 June	6	10	16

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter