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MiR-135a-5p suppresses breast cancer cell proliferation, migration, and invasion by regulating BAG3
Hongxu Zhanga, Minghui Wanga, Zhiqiang Langb, Haiwang Liuc, Jianping Liua, Lihui Maa,
Corresponding author
malihui3939@sina.com

Corresponding author.
a Departments of Breast Surgery, Affiliated Hospital of Chengde Medical University, Hebei, China
b Medical Research Center, Xi'an No.3 Hospital, Shaanxi, China.
c Department of Pathology, Affiliated Hospital of Chengde Medical University, Hebei, China
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Introduction</span><p id="para0008" class="elsevierStylePara elsevierViewall">Breast Cancer &#40;BC&#41; is one of the most common malignancies in females&#46;<a class="elsevierStyleCrossRefs" href="#bib0001"><span class="elsevierStyleSup">1-3</span></a> The targeted therapy&#44; an emerging treatment in addition to surgery&#44; radiotherapy and chemotherapy&#44; has the advantages of strong specificity&#44; significant efficacy&#44; low toxicity and side effects&#44; improving the prognosis of the patients&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> With the deepening of molecular biology research&#44; breakthrough progress has been made in exploring the potential targets of BC&#46;</p><p id="para0009" class="elsevierStylePara elsevierViewall">MicroRNA &#40;miRNAs&#41; are non-coding small RNA transcripts consisting of&#160;17&#8211;25&#160;<span class="elsevierStyleItalic">nt</span> that complement the 3&#8242;UTR of a specific target mRNA&#44; resulting in mRNA degradation and translation inhibition&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> MiRNAs can function as tumor promoters or suppressors&#44; and they are considered as promising therapeutic targets for cancers&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> The dysregulation of miRNAs is closely associated with the malignant biological behaviors of BC cells such as growth&#44; apoptosis&#44; invasion and angiogenesis&#46;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> MiR-135a-5p partakes in the progression of a variety of malignancies&#46; For example&#44; miR-135a-5p overexpression restrains the growth and invasion of SW620&#160;cells&#44; and induces apoptosis&#59;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> miR-135a-5p is significantly inhibited in glioma tissues&#44; and miR-135a-5p overexpression reduces the growth of glioma xenografts in mouse&#46;<a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> However&#44; its biological function and mechanism in BC deserve further investigation&#46;</p><p id="para0010" class="elsevierStylePara elsevierViewall">Bcl-2 Associated Athanogene&#160;3 &#40;BAG3&#41; is overexpressed in several tumors&#44; and it is related to the growth&#44; invasion&#44; metastasis&#44; drug resistance of tumor cells&#44; and prognosis of the patients&#44; making BAG3 a potential therapeutic target&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> Reportedly&#44; BAG3 is highly expressed in the tumor tissues of patients with BC&#44; and its high expression indicates a poor prognosis of the patients&#59; knocking down BAG3 significantly suppresses the growth and migration of BC cells&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a></p><p id="para0011" class="elsevierStylePara elsevierViewall">This study is an in vitro study&#46; We investigated the expression characteristics&#44; biological function and underlying mechanism of miR-135a-5p&#46; In this work&#44; bioinformatics analysis suggested that miR-135a-5p was lowly expressed in BC tissues&#44; and BAG3 may be a target of miR-135a-5p&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Materials and methods</span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Tissue sample collection</span><p id="para0012" class="elsevierStylePara elsevierViewall">49&#160;BC patients admitted to Xi&#39;an No&#46;3 Hospital from July&#160;2017 to November&#160;2021 were selected&#44; and the surgically removed cancer tissues and corresponding para-cancer tissues were collected&#46; The samples were stored in liquid nitrogen within&#160;30&#160;min after collection&#46; All the individuals were not treated with radiotherapy&#44; chemotherapy&#44; and other related anti-cancer treatments before surgery&#46; This work&#44; with signed informed consent forms&#44; was approved by the ethics committee of the hospital &#40;2017YHDYY012&#41; and all experiments were conducted according to the Declaration of Helsinki&#46;</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">Cell culture</span><p id="para0013" class="elsevierStylePara elsevierViewall">BC cell lines &#40;MCF-7&#44; MDA-MB-231&#44; MDA-MB-468 and DU4475&#41; and HEK-293 cells were obtained from American Type Culture Collection &#40;Manassas&#44; VA&#44; USA&#41;&#46; Immortalized human mammary epithelial cells MCF-12A were obtained from BeNa Culture Collection &#40;Beijing&#44; China&#41;&#46; These cells were cultured in Roswell Park Memorial Institute Medium&#160;1640 &#40;RPMI-1640&#44; Gibco&#44; Carlsbad&#44; CA&#44; USA&#41; containing&#160;10&#37;&#160;fetal bovine serum &#40;FBS&#59; HyClone&#44; Logan&#44; UT&#44; USA&#41;&#44; 100&#160;U&#47;ml penicillin &#40;Invitrogen&#44; Carlsbad&#44; CA&#44; USA&#41; and 100&#160;&#956;g&#47;mL streptomycin &#40;Gibco&#44; Waltham&#44; MA&#44; USA&#41; at&#160;37&#160;&#176;C in&#160;5&#37; CO<span class="elsevierStyleInf">2</span>&#46; Once reaching about&#160;90&#37;&#160;confluence&#44; the cells were trypsinized with&#160;0&#46;25&#37;&#160;trypsin &#40;Roche&#44; Basel&#44; Switzerland&#41; for passage&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Cell transfection</span><p id="para0014" class="elsevierStylePara elsevierViewall">MDA-MB-231 and MCF-7 cells in the logarithmic growth phase were trypsinized with trypsin&#44; inoculated into six-well plates at&#160;1&#160;&#215;&#160;10<span class="elsevierStyleSup">6</span> cells&#47;well&#44; and cultured overnight&#46; Subsequently&#44; the transfection was performed&#46; MiRNA mimics control &#40;miR-NC&#41;&#44; miR-135a-5p mimics &#40;miR mimics&#41;&#44; miR-135a-5p inhibitors &#40;miR inhibitors&#41; and its Negative Control &#40;inh-NC&#41;&#44; empty plasmid &#40;NC&#41;&#44; BAG3 overexpression plasmid &#40;BAG3&#41;&#44; small interfering RNA targeting BAG3 &#40;si-BAG3&#41; and control siRNA Negative Control &#40;si-NC&#41; were transfected into MDA-MB-231 and MCF-7 cells according to the manufacturer&#39;s instructions of Lipofectamine&#8482; 2000&#160;kit &#40;Invitrogen&#44; Carlsbad&#44; CA&#44; USA&#41;&#46; The above oligonucleotides and plasmids were available from RiboBio Co&#44; Ltd&#46; &#40;Guangzhou&#44; China&#41;&#46; 48h&#160;later&#44; the transfection efficiency was validated by quantitative Real-time PCR &#40;qRT-PCR&#41;&#44; and then the cells were collected for further analysis&#46;</p></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013">qRT-PCR</span><p id="para0015" class="elsevierStylePara elsevierViewall">The total RNA of tissue samples and cells was extracted using TRIzol reagent &#40;Invitrogen&#44; Shanghai&#44; China&#41; and reversely transcribed by a reverse transcription kit &#40;Qiagen&#44; Hilden&#44; Germany&#41; to generate cDNA&#46; Reverse transcription conditions&#58; 16&#160;&#176;C&#44; 30&#160;min&#59; 42&#176;&#44; 30&#160;min&#59; 75&#160;&#176;C&#44; 15&#160;min&#46; With cDNA as the template&#44; qRT-PCR was then performed with a SYBR Premix-EX-TAQ &#40;Takara&#44; Tokyo&#44; Japan&#41; on an ABI7300 system &#40;Thermo Fisher Scientific&#44; Waltham&#44; MA&#44; USA&#41;&#46; GAPDH or U6 was used as an internal control for mRNA or miRNA respectively&#46; Primer sequences&#58; miR-135a-5p&#58; 5&#8242;-TTGGTCTTGTTTCCCGGTCC-3&#8242; &#40;forward&#41;&#44; 5&#8242;-TCACAGCTCCACAGGCTAAC-3&#8242; &#40;reverse&#41;&#59; BAG3&#58; 5&#8242;-CAACAGCCGCACCACTAC-3&#8242;&#40;forward&#41;&#44; 5&#8242;-CATTGGCAGAGGATGGAGTC-3&#8242; &#40;reverse&#41;&#59; U6&#58; 5&#8242;-CTAGCTTCGGCAGCACA-3&#8242;&#40;forward&#41;&#44; 5&#8242;-AACGCTTCACGAATTTGCGT-3&#8242; &#40;reverse&#41;&#59; GAPDH&#58; 5&#8242;-ACAGTCAGCCGCATCTTCTT-3&#8242; &#40;forward&#41;&#44; 5&#8242;-AAATGAGCCCCAGCCTTCTC-3&#8242; &#40;reverse&#41;&#46; The PCR amplification conditions&#58; 95&#160;&#176;C&#44; 2&#160;min&#59; 95&#160;&#176;C&#44; 15&#160;s&#59; 72&#160;&#176;C&#44; 35&#160;s for&#160;35&#160;cycles&#46; The Cycle Threshold &#40;CT&#41; values were recorded&#44; and the relative expression of miR-135a-5p and BAG3 mRNA were calculated by&#160;2<span class="elsevierStyleSup">&#8722;&#916;&#916;Ct</span> method&#46;</p></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014">Cell counting kit-8 &#40;CCK-8&#41; assay</span><p id="para0016" class="elsevierStylePara elsevierViewall">After transfection&#44; MDA-MB-231 and MCF-7 cells were inoculated in&#160;96-well plates with&#160;2000&#160;cells per well and cultured for&#160;24&#160;h&#46; According to the manufacturer&#39;s instruction&#44; 10&#160;&#956;L of CCK-8 reagents &#40;Med Chem Express&#44; Monmouth Junction&#44; NJ&#44; USA&#41; were added to each well at the 24th h&#44; 48th h and 72nd h&#44; and then the cells were incubated for an additional&#160;1&#160;h&#46; The absorbance &#40;OD&#41; values of each well at&#160;450&#160;nm wavelength were detected at each indicated time point by a microplate reader &#40;Bio-Rad&#44; Hercules&#44; CA&#44; USA&#41;&#46;</p></span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0015">BrdU assay</span><p id="para0017" class="elsevierStylePara elsevierViewall">MDA-MB-231 and MCF-7 cells were inoculated into&#160;24-well plates &#40;with a cover glass inside&#41; at 2&#46;5&#160;&#215;&#160;10<span class="elsevierStyleSup">5</span>&#160;cells&#47;well&#46; 24&#160;h later&#44; BrdU solution &#40;Beyotime Biotechnology&#44; Shanghai&#44; China&#41; was loaded&#44; followed by incubation for&#160;4&#160;h&#46; Subsequently&#44; the cells were fixed with&#160;4&#37; paraformaldehyde for&#160;30&#160;min&#46; Next&#44; the cells were stained with&#160;100&#160;&#956;L of&#160;1&#160;&#215;&#160;Apollo for&#160;30&#160;min&#46; Next&#44; l&#160;g&#47;mL DAPI staining solution was dripped into each well for incubation in darkness for&#160;20&#160;min at ambient temperature&#46; The cells were washed with Phosphate Buffer Saline &#40;PBS&#41;&#44; and the total number of cells and the number of BrdU-positive cells in the randomly chosen&#160;10&#160;high-power fields were counted under a microscope&#46; The positive rate of BrdU staining was then calculated&#46;</p></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0016">Transwell assay</span><p id="para0018" class="elsevierStylePara elsevierViewall">Transfected MDA-MB-231 and MCF-7 cells were trypsinized with trypsin and followingly centrifuged at&#160;500&#160;&#215;&#160;g for&#160;5&#160;min to collect the cells&#46; After the cell density was adjusted with a serum-free medium&#44; a cell suspension of&#160;1&#160;&#215;&#160;10<span class="elsevierStyleSup">5</span>&#160;cells&#47;mL was prepared&#46; In the migration assay&#44; 100&#160;&#956;L of cell suspension was added into the upper compartment of the transwell chamber &#40;8&#160;&#956;m pore size&#41;&#44; and 650&#160;&#956;L of medium with&#160;10&#37; FBS was added into the lower compartment&#44; and the cells were cultured in&#160;5&#37; CO<span class="elsevierStyleInf">2</span> at&#160;37&#160;&#176;C for&#160;24&#160;h&#46; Next&#44; the chambers were taken out&#44; and the cells on the upper surface of the microporous membrane were wiped off with a cotton swab&#46; The chamber was carefully rinsed with PBS two times&#44; and the cells on the lower side of the microporous membrane were fixed with&#160;4&#37; paraformaldehyde for&#160;15&#160;min&#44; and then stained with&#160;0&#46;1&#37;&#160;crystal violet for&#160;20&#160;min&#46; Next&#44; the chamber was immersed in PBS&#44; and air-dried&#46; The cells were observed under a microscope&#44; and the number of cells was counted&#46; For the invasion assay&#44; the microporous membrane was covered with a layer of Matrigel&#44; and the remaining steps were the same as those in the migration assay&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0017">Flow cytometry</span><p id="para0019" class="elsevierStylePara elsevierViewall">The transfected cells were inoculated into a&#160;6-well plate &#40;1&#160;&#215;&#160;10<span class="elsevierStyleSup">5</span>&#160;cells&#47;well&#41; and cultured overnight&#44; and then the cells were trypsinized with trypsin&#44; washed with Phosphate Buffer Saline &#40;PBS&#41;&#44; harvested&#44; and re-suspended in&#160;300&#160;&#956;L of binding solution&#46; Then the cells were mixed with and incubated with&#160;10&#160;&#956;L of Annexin V-FITC staining solution &#40;BD Bioscience&#44; San Diego&#44; CA&#44; USA&#41; for&#160;15&#160;min in the darkness at ambient temperature&#46; Then&#44; 5&#160;&#956;L of Propidium Iodide &#40;PI&#41; staining solution &#40;BD Bioscience&#44; San Diego&#44; CA&#44; USA&#41; was added for staining the cells for&#160;5&#160;min in darkness&#46; Finally&#44; the cells were washed with PBS&#44; and the apoptosis of the transfected cells was detected by a flow cytometer&#46;</p></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0018">Dual-luciferase gene reporter assay</span><p id="para0020xg" class="elsevierStylePara elsevierViewall">The binding site between miR-135a-5p and BAG3 3&#8242;UTR was predicted by bio information&#46; A fragment with the binding site for miR-135a-5p of BAG3 mRNA 3&#8242;UTR was amplified by PCR and followingly inserted into a pMIR-REPORT luciferase vector &#40;Ambion&#44; Frederick&#44; MD&#44; USA&#41; to construct a BAG3 Wild-Type plasmid &#40;WT-BAG3&#41;&#46; Then&#44; partial nucleotides at the binding site were mutated by Gene Mapping Techniques to construct a mutated reporter plasmid &#40;MUT-BAG3&#41;&#46; HEK-293 cells were co-transfected with the reporter plasmids and miR-mimics &#40;or miR-inhibitors&#41; or miR-NC &#40;or inh-NC&#41; to verify the binding relationship between miR-135a-5p and BAG3 mRNA 3&#8242;UTR&#46; 36&#160;h later&#44; according to the manufacturer&#39;s instructions of the luciferase activity detection kit &#40;Ambion&#44; Frederick&#44; MD&#44; USA&#41;&#44; the relative luciferase activity of the cells in each group was detected&#44; expressed as the ratio of the firefly luciferase activity to the Renilla luciferase activity&#46;</p></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019">Western blot</span><p id="para0021" class="elsevierStylePara elsevierViewall">The transfected BC cells were harvested&#44; and the total protein was extracted by ice-cold RIPA lysis buffer &#40;Pierce&#44; Rockford&#44; IL&#44; USA&#41;&#46; The protein was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and followingly transferred to polyvinylidene fluoride membranes&#44; which were blocked with&#160;5&#37; skimmed milk for&#160;1&#160;h at room temperature&#44; and then the membranes were incubated with primary recombinant anti-BAG3 antibody &#40;ab92309&#44; 1&#58;1000&#44; Abcam&#44; Shanghai&#44; China&#41; for&#160;2&#160;h at room temperature&#46; The membranes were then washed and then incubated with goat-anti-rabbit IgG H&#38;L &#40;ab216773&#44; 1&#58;5000&#44; Abcam&#44; Shanghai&#44; China&#41; for&#160;1&#46;5&#160;h at room temperature&#44; followed by washing again&#46; Finally&#44; the protein bands were developed by the enhanced chemiluminescence detection reagent &#40;Beyotime&#44; Shanghai&#44; China&#41;&#44; and analyzed by a gel imaging system&#46; The ratio of the density of target protein to the density of the internal reference was taken as the relative expression of the target protein&#46;</p></span><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0020">Statistical analysis</span><p id="para0022" class="elsevierStylePara elsevierViewall">SPSS&#160;22&#46;0 software was adopted for data analysis&#46; The data conformed to normal distribution were expressed as &#8220;<span class="elsevierStyleItalic">x</span>&#160;&#177;&#160;s<span class="elsevierStyleItalic">&#8221;</span>&#46; The student&#39;s <span class="elsevierStyleItalic">t</span>-test was executed for comparisons between two groups&#44; and a one-way analysis of variance was conducted for the comparisons among multiple groups&#46; The correlation analysis was performed with Pearson&#39;s correlation analysis&#59; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;05 is indicative of a statistically significant difference&#46;</p></span></span><span id="sec0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0021">Results</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0022">Expression characteristics of miR-135a-5p in BC</span><p id="para0023" class="elsevierStylePara elsevierViewall">Gene Expression Omnibus &#40;GEO&#41; database showed that 339&#160;miRNAs were down-regulated&#44; and 1492&#160;miRNAs were up-regulated in dataset GSE80038&#59; in dataset GSE45666&#44; 1285 miRNAs were down-regulated and 394&#160;miRNAs were up-regulated&#59; in dataset GSE38167&#44; 343&#160;miRNAs were down-regulated and 378&#160;miRNAs were up-regulated&#44; of which&#44; miR-135a-5p was markedly inhibited in BC tissues in all of the three datasets &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>A-C&#41;&#46; qRT-PCR showed that miR-135a-5p expression in cancer tissues of BC patients was down-regulated compared with that in the normal group &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>D&#41;&#46; Moreover&#44; miR-135a-5p expression was down-regulated in BC sample of&#160;95&#46;9&#37;&#160;cases&#160;&#40;47&#160;of&#160;49&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>E&#41;&#46; Receiver Operating Characteristic &#40;ROC&#41; curve analysis suggested that miR-135a-5p could be considered as a discriminative biomarker for BC with&#160;85&#46;71&#37;&#160;sensitivity and 81&#46;63&#37;&#160;specificity in the optimal cutoff value&#160;&#61;&#160;0&#46;6069 &#40;AUC&#160;&#61;&#160;0&#46;872&#59; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;001&#41;&#44; &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>F&#41;&#46; In addition&#44; low expression of miR-135a-5p was associated with lymph node metastasis and higher TNM stage of the patients &#40;<span class="elsevierStyleItalic">p</span> &#60; 0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#41;&#46; In addition&#44; the OncomiR database showed that low miR-135a-5p was significantly associated with short overall survival in patients &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>G&#41;&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><elsevierMultimedia ident="tbl0001"></elsevierMultimedia></span><span id="sec0016" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0023">The biological function of miR-135a-5p in BC</span><p id="para0024" class="elsevierStylePara elsevierViewall">Compared with MCF-12A&#44; miR-135a-5p expression in the BC cell lines &#40;MCF-7&#44; MDA-MB-231&#44; MDA-MB-468&#44; DU4475&#41; was significantly down-regulated &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>A&#41;&#46; Among the five BC cell lines&#44; miR-135a-5p expression in MDA-MB-231 cells was the lowest&#44; while that of MCF-7 cells was the highest&#46; Therefore&#44; we transfected miR-mimics &#40;or miR-NC&#41; and miR-inhibitors &#40;or NC-inhibitors&#41; into MDA-MB-231 cells and MCF-7 cells&#44; respectively&#44; to construct the cell models with miR-135a-5p overexpression or inhibition&#44; with qRT-PCR testifying it a success &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>B&#41;&#46; CCK-8 assay showed that as against the control&#44; miR-135a-5p overexpression suppressed the viability of MDA-MB-231 cells while inhibiting miR-135a-5p promoted the cell viability of MCF-7 &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>C&#41;&#46; Next&#44; BrdU assay&#44; transwell assay&#44; and flow cytometry showed that miR-135a-5p overexpression restrained the growth&#44; migration&#44; and invasion of BC cells and arrested the cell cycle progression at G0&#47;G1 phase&#59; inhibiting miR-135a-5p had the opposite effect &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>D-G&#41;&#46;</p><elsevierMultimedia ident="fig0002"></elsevierMultimedia></span><span id="sec0017" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0024">BAG3 is a downstream target of miR-135a-5p</span><p id="para0025" class="elsevierStylePara elsevierViewall">We then identified the subcellular localization of miR-135a-5p in MDA-MB-231 and MCF-7 cells by qRT-PCR and found that miR-135a-5p was mainly present in the cytoplasm of BC cells&#44; suggesting it may regulate gene expression at the post-transcriptional level &#40;<a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>A&#41;&#46; To expound the mechanism of miR-135a-5p&#44; StarBase database was searched&#44; and the downstream genes of miR-135a-5p were analyzed by DAVID database&#46; Kyoto Encyclopedia of Genes and Genomes &#40;KEGG&#41; enrichment analysis showed that the above target genes were involved in the p53&#44; Hippo&#44; and Wnt signaling pathways&#44; all of which were associated with cancer biology &#40;<a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>B&#41;&#46; Gene Ontology &#40;GO&#41; analysis showed that the above target genes were significantly enriched in biological processes such as cell division and protein transport&#59; they were also enriched in cellular components including intercellular bridge and nucleus&#44; etc&#46;&#59; and in molecular functions including protein complex binding and protein tyrosine phosphatase activity &#40;<a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>C&#41;&#46; Among the candidate targets&#44; BAG3&#44; which is closely associated with BC progression&#44; attracted the authors&#8217; attention&#44; and the binding sequence was shown in <a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>D&#46; Subsequently&#44; dual luciferase reporter gene assay showed that up-regulating miR-135a-5p remarkably suppressed the luciferase activity of WT-BAG3 reporter and inhibiting miR-135a-5p significantly increased the activity of WT-BAG3 reporter&#44; while that of MUT-BAG3 group was not significantly impacted by miR-135a-5p &#40;<a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>E&#41;&#46; Western blot showed that miR-135a-5p overexpression down-regulated BAG3 expression&#44; while its inhibition functioned oppositely &#40;<a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>F&#41;&#46; Through qRT-PCR&#44; we observed that BAG3 mRNA expression in BC tissues was increased compared with that in the control group &#40;<a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>G&#41;&#44; and BAG3 mRNA expression was increased in 95&#46;9&#37;&#160;cases &#40;47&#160;of&#160;49&#160;cases&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0004">Fig&#46; 4</a>H&#41;&#44; and BAG3 mRNA was negatively correlated with miR-135a-5p expression in BC samples &#40;<a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>I&#41;&#46;</p><elsevierMultimedia ident="fig0003"></elsevierMultimedia><elsevierMultimedia ident="fig0004"></elsevierMultimedia></span><span id="sec0018" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0025">BAG3 counteracts the impact of miR-135a-5p on the biological behaviors of BC cells</span><p id="para0026" class="elsevierStylePara elsevierViewall">To further explore the effects of miR-135a-5p and BAG3 on the growth&#44; migration&#44; invasion&#44; and cell cycle progression of BC cells&#44; miR-NC&#44; miR mimics&#44; miR mimics&#43;BAG3 and inh-NC&#44; miR inhibitors&#44; and miR inhibitors&#43;si-BAG3 were co-transfected into MDA-MB-231 and MCF-7 cells&#44; respectively&#44; with qRT-PCR assay showing it a success &#40;<a class="elsevierStyleCrossRef" href="#fig0004">Fig&#46; 4</a>A&#41;&#46; CCK-8 assay&#44; BrdU assay&#44; wound healing assay&#44; transwell assay and flow cytometry assay showed that miR-135a-5p overexpression significantly inhibited cell growth&#44; migration&#44; and invasion and blocked cell cycle progression in G0&#47;G1 phase compared with the control group&#44; and overexpressing BAG3 reversed these effects&#59; miR-135a-5p inhibition remarkably promoted the malignant biological behaviors of BC cells&#44; while silencing BAG3 counteracted these effects &#40;<a class="elsevierStyleCrossRef" href="#fig0004">Fig&#46; 4</a>B-F&#41;&#46;</p></span><span id="sec0019" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0026">BAG3 activates the cell cycle&#44; mTOR&#44; and TGF-&#946; signaling pathway</span><p id="para0027" class="elsevierStylePara elsevierViewall">To further clarify how miR-135a-5p&#47;BAG3 axis regulates the biological behaviors of BC cells&#44; we used Gene Set Enrichment Analysis &#40;GSEA&#41; to predict the signaling pathways possibly associated with BAG3&#46; The results showed that the high expression of BAG3 was positively associated with the activation of the cell cycle&#44; mTOR and TGF-&#946; signaling pathways &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 5</a>A-C&#41;&#46; Subsequently&#44; Western blot was showed that overexpression of BAG3 up-regulated the expressions of mTOR and TGF-&#946;1&#44; and miR-135a-5p overexpression blocked these effects&#59; knockdown of BAG3 down-regulated the expression of mTOR and TGF-&#946;1&#44; while inhibition of miR-135a-5p worked oppositely &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 5</a>D&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0027">Discussion</span><p id="para0028" class="elsevierStylePara elsevierViewall">The tumorigenesis and progression of BC involve the activation of proto-oncogenes and the inactivation of tumor suppressors&#44; followed by the dysregulation of signal pathways&#44; and finally the change of phenotypes of cells&#46;<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> MiRNAs are conceptually a group of endogenous short non-coding RNA transcripts&#44; which are involved in biological processes such as cell growth&#44; apoptosis&#44; and differentiation&#46;<a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> MiR-135a-5p has different expression patterns in different cancers&#58; high expression of miR-135a-5p in colon cancer tissues is associated with unfavorable clinicopathologic indexes of the patients&#59; inhibiting miR-135a-5p suppresses the growth&#44; migration&#44; and invasion of SW620 cells&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> However&#44; miR-135a-5p is under-expressed in head and neck squamous cell carcinoma&#44; which is closely related to the poor prognosis of the patients&#59; miR-135a-5p overexpression targets HOXA10&#44; thereby inhibiting tumor cell growth and promoting the apoptosis&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> In nasopharyngeal carcinoma&#44; miR-135a-5p expression is also reduced&#59; miR-135a-5p is negatively regulated by lncRNA FOXD3-AS1&#44; and inhibiting miR-135a-5p can significantly promote the viability and inhibit the apoptosis of nasopharyngeal carcinoma cells&#46;<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a> Here we found that miR-135a-5p expression was reduced in BC tissues&#44; which was closely associated with the poor prognosis of the patients&#46; Additionally&#44; miR-135a-5p overexpression inhibited the malignant biological behaviors of BC cells&#44; while miR-135a-5p inhibition exerted the opposite effects&#46; The present data suggest that miR-135a-5p may serve as a tumor suppressor in BC&#46;</p><p id="para0029" class="elsevierStylePara elsevierViewall">In eukaryotes&#44; autophagy is a highly conservative catabolism process in which cells degrade intracellular substances&#44; organelles&#44; or proteins through lysosomes and recycle various cytoplasmic components to provide energy and substrates for biosynthesis&#46;<a class="elsevierStyleCrossRef" href="#bib0017"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0018"><span class="elsevierStyleSup">18</span></a> Moreover&#44; autophagy is quietly vital in the maintenance of cell homeostasis&#44; cell differentiation&#44; growth and development&#44; and stress response&#44; and the dysregulation of autophagy is associated with the pathogenesis of a lot of human diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0017"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0018"><span class="elsevierStyleSup">18</span></a> As the regulatory molecule of autophagy&#44; BAG3 plays a vital role in maintaining cell homeostasis&#44; which has attracted extensive attention in recent years&#44; especially in cancer biology&#46;<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> One of the important functions of BAG3 is to degrade misfolded proteins or protein aggregates by regulating selective macroautophagy&#47;autophagy under stress conditions&#44; thereby maintaining protein homeostasis&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a> and it is involved in a series of physiological and pathological processes including growth&#44; apoptosis&#44; adhesion&#44; and viral replication&#46;<a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a> Some previous studies have shown that in some human malignancies&#44; such as thyroid cancer&#44;<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a> cervical cancer&#44;<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a> ovarian cancer&#44;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a> BAG3 is abnormally expressed&#44; and it can modulate the progression of the disease&#46; For example&#44; BAG3 is abnormally highly expressed in ovarian cancer tissues and cells&#44; and the knock-down of BAG3 suppresses the viability of tumor cell&#44; enhances the sensitivity of tumor cells to Olaparib&#44; and synergistically kills ovarian cancer cells in vitro with Olaparib via modulating autophagy&#46;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a> In addition&#44; there are some previous studies on BAG3 in BC&#46; For example&#44; in BC&#44; BAG3 up-regulates the expression levels of Bcl-2 and Bcl-xL by targeting HSP70&#47;Mcl-1 signaling pathway and suppresses the chemoresistance of tumor cells&#44; indicating that BAG3 may be a potential target for treating BC&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> Additionally&#44; high expression of BAG3 in triple-negative BC is associated with poor prognosis of patients&#44; and BAG3 regulates PI3K&#47;AKT and FAK&#47;Src pathways to promote the proliferation&#44; migration&#44; and invasion of triple-negative BC cells&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> In the present work&#44; we found that BAG3 was the downstream target of miR-135a-5p&#46; miR-135a-5p specifically modulated BAG3 in BC cells&#44; further regulating mTOR and TGF-&#946; pathways&#46; These data partly explain the mechanism of BAG3 dysregulation in BC tissues&#47;cells&#46;</p><p id="para0030" class="elsevierStylePara elsevierViewall">In summary&#44; miR-135a-5p expression is reduced in BC and its expression level is associated with the prognosis of patients&#46; Additionally&#44; miR-135a-5p negatively regulates BAG3 expression&#44; inhibits mTOR and TGF-&#946; pathways&#44; and restrains the growth&#44; migration&#44; and invasion of BC cells&#46; This study suggests that miR-135a-5p may be a potential biomarker and therapeutic target for the diagnosis and treatment of BC&#46;</p></span><span id="sec0021" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0028">Author&#39;s contribution</span><p id="para0031" class="elsevierStylePara elsevierViewall">Conceived and designed the experiments&#58; Zhiqiang Lang&#44; Hongxu Zhang&#44; Lihui Ma&#46;</p><p id="para0032" class="elsevierStylePara elsevierViewall">Performed the experiments&#58; Zhiqiang Lang&#44; Haiwang Liu&#46;</p><p id="para0033" class="elsevierStylePara elsevierViewall">Analyzed the data&#58; Hongxu Zhang&#44; Minghui Wang&#44; Jianping Liu&#46;</p><p id="para0034" class="elsevierStylePara elsevierViewall">Wrote the paper&#58; Hongxu Zhang&#44; Minghui Wang&#44; Zhiqiang Lang&#46;</p><p id="para0035" class="elsevierStylePara elsevierViewall">All authors read and approved the final manuscript&#46;</p></span><span id="sec0023" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0030">Ethics statement</span><p id="para0037" class="elsevierStylePara elsevierViewall">The present study was approved by the Ethics Review Board of Xi&#39;an No&#46;3 Hospital &#40;Ethics committee number&#58; 2017YHDYY012&#41;&#46;</p></span><span id="sec0024" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0031">Data availability statement</span><p id="para0038" class="elsevierStylePara elsevierViewall">The data used to support the findings of this study are available from the corresponding author upon request&#46;</p></span></span>"
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              "titulo" => "Background"
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        3 => array:2 [
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          "titulo" => "Introduction"
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          "titulo" => "Materials and methods"
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            0 => array:2 [
              "identificador" => "sec0003"
              "titulo" => "Tissue sample collection"
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              "titulo" => "Cell transfection"
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              "titulo" => "qRT-PCR"
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              "titulo" => "Cell counting kit-8 &#40;CCK-8&#41; assay"
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              "titulo" => "BrdU assay"
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              "titulo" => "Flow cytometry"
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              "titulo" => "Western blot"
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          "titulo" => "Results"
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              "identificador" => "sec0015"
              "titulo" => "Expression characteristics of miR-135a-5p in BC"
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            1 => array:2 [
              "identificador" => "sec0016"
              "titulo" => "The biological function of miR-135a-5p in BC"
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              "identificador" => "sec0017"
              "titulo" => "BAG3 is a downstream target of miR-135a-5p"
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              "identificador" => "sec0018"
              "titulo" => "BAG3 counteracts the impact of miR-135a-5p on the biological behaviors of BC cells"
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              "identificador" => "sec0019"
              "titulo" => "BAG3 activates the cell cycle&#44; mTOR&#44; and TGF-&#946; signaling pathway"
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          "titulo" => "Discussion"
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          "titulo" => "Data availability statement"
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          "identificador" => "xack684950"
          "titulo" => "Acknowledgement"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2022-06-10"
    "fechaAceptado" => "2022-09-05"
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        0 => array:4 [
          "clase" => "keyword"
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          "palabras" => array:5 [
            0 => "Breast cancer"
            1 => "Mir-135a-5p"
            2 => "Bag3"
            3 => "Proliferation"
            4 => "Migration"
          ]
        ]
      ]
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    "highlights" => array:2 [
      "titulo" => "Highlights"
      "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><p id="spara008" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">&#8226;</span><p id="para0001" class="elsevierStylePara elsevierViewall">MiR-135a-5p was significantly down-regulated and BAG3 expression was significantly raised in BC tissues&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0002"><span class="elsevierStyleLabel">&#8226;</span><p id="para0002" class="elsevierStylePara elsevierViewall">MiR-135a-5p overexpression inhibited the viability&#44; migration and aggressiveness of BC cells&#44; and blocked cell cycle progression in G0&#47;G1 phase&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0003"><span class="elsevierStyleLabel">&#8226;</span><p id="para0003" class="elsevierStylePara elsevierViewall">Over-expression of BAG3 reversed the impacts of miR-135a-5p on BC cells&#46;</p></li></ul></p></span>"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Background</span><p id="spara009" class="elsevierStyleSimplePara elsevierViewall">MicroRNAs &#40;miRNAs&#41; are involved in the progression of diverse human cancers&#46; This work aimed to delve into how microRNA-135a-5p &#40;miR-135a-5p&#41; affects the biological behaviors of Breast Cancer &#40;BC&#41; cells&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Methods</span><p id="spara010" class="elsevierStyleSimplePara elsevierViewall">Gene Expression Omnibus &#40;GEO&#41; datasets were used to analyze the expression differences of miR-135a-5p in cancer tissues of BC patients&#46; Quantitative real-time PCR and western blot were conducted to detect miR-135a-5p and Bcl-2 Associated Athanogene &#40;BAG3&#41; expression levels in BC tissues and cells&#44; respectively&#46; The proliferation&#44; migration&#44; invasion&#44; and cell cycle of BC cells were detected by cell counting kit-8 assay&#44; BrdU assay&#44; wound healing assay&#44; transwell assay&#44; and flow cytometry&#46; The targeted relationship between miR-135a-5p and BAG3 mRNA 3&#8242;UTR predicted by bioinformatics was further testified by a dual-luciferase reporter gene assay&#46; Pearson&#39;s correlation analysis was adopted to analyze the correlation between miR-135a-5p expression and BAG3 expression&#46; The downstream pathways of BAG3 were analyzed by the LinkedOmics database&#46;</p></span> <span id="abss0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Results</span><p id="spara011" class="elsevierStyleSimplePara elsevierViewall">MiR-135a-5p was significantly down-regulated and BAG3 expression was significantly raised in BC tissues&#46; MiR-135a-5p overexpression repressed the viability&#44; migration and invasion of BC cells&#44; and blocked cell cycle progression in G0&#47;G1 phase while inhibiting miR-135a-5p worked oppositely&#46; BAG3 was verified as a target of miR-135a-5p&#46; Overexpression of BAG3 reversed the impacts of miR-135a-5p on the malignant biological behaviors of BC cells&#46; The high expression of BAG3 was associated with the activation of the cell cycle&#44; mTOR and TGF-&#946; signaling pathways&#46;</p></span> <span id="abss0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0006">Conclusion</span><p id="spara012" class="elsevierStyleSimplePara elsevierViewall">MiR-135a-5p regulates BAG3 to repress the growth&#44; migration&#44; invasion&#44; and cell cycle progression of BC cells&#46;</p></span>"
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          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Expression characteristics of miR-135a-5p in tissues of BC patients and BC cells&#46;</span> &#40;A&#8210;C&#41; The microarray datasets GSE80038&#44; GSE45666 and GSE38167 were downloaded from the GEO database to analyze the expression differences of miRNA&#44; and the volcano map was used to display the differentially expressed miRNAs in the BC samples vs&#46; normal tissue samples&#46; &#40;D&#44; E&#41; The expression of miR-135a-5p in the cancer tissues and normal tissues of&#160;49&#160;BC patients was detected by qRT-PCR&#46; &#40;F&#41; ROC curve analysis showed the diagnostic accuracy of miR-135a-5p&#46; &#40;G&#41; OncomiR database was used to analyze the relationship between the expression of miR-135a-5p and the overall survival of patients with BC&#46; &#42;<span class="elsevierStyleItalic">p</span> &#60; 0&#46;05&#44; &#42;&#42; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;01&#44; and &#42;&#42;&#42; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;001&#46;</p>"
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          "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Impacts of miR-135a-5p on the proliferation&#44; migration&#44; invasion and cell cycle progression of BC cell&#46;</span> &#40;A&#41; The expression of miR-135a-5p in immortalized mammary epithelial cells and BC cell lines was detected by qRT-PCR&#46; &#40;B&#41; miR-NC&#44; miR-mimics and inh-NC&#44; and miR-inhibitors were transfected into MDA-MB-231&#160;cells and MCF-7&#160;cells&#44; respectively&#44; and the transfection efficiency was detected by qRT-PCR&#46; &#40;C&#41; After transfection&#44; MDA-MB-231 and MCF-7 cells were tested for the viability by CCK-8 assay&#46; &#40;D&#41; After transfection&#44; the proliferation of MDA-MB-231 and MCF-7 cells was detected by BrdU method&#46; &#40;E&#44; F&#41; Changes in the migration and invasion abilities of MDA-MB-231 and MCF-7 cells after transfection were detected by wound healing assay and Transwell assay&#46; &#40;G&#41; Changes in the cell cycle distribution of MDA-MB-231 and MCF-7 cells were detected by flow cytometry after transfection&#46; &#42; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;05&#44; &#42;&#42; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;01&#44; and &#42;&#42;&#42; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;001&#46;</p>"
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          "en" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">BAG3 is a direct downstream target of miR-135a-5p&#46;</span> &#40;A&#41; The subcellular localization of miR-135a-5p was detected by qRT-PCR in BC cells&#46; &#40;B&#41; KEGG pathway analysis of the downstream target genes of miR-135a-5p&#46; &#40;C&#41; GO enrichment analysis of the downstream target genes of miR-135a-5p&#46; &#40;D&#41; The binding sequence of BAG3 mRNA 3&#8242; UTR wild-type and mutant sequences with miR-135a-5p&#46; &#40;E&#41; The effect of the miR-135a-5p overexpression on the luciferase activities of WT-BAG3 and MUT-BAG3 was verified by dual luciferase reporter gene assay&#46; &#40;F&#41; Western blot was used to detect the effect of the overexpression or inhibition of miR-135a-5p on the expression of BAG3 protein&#46; &#40;G&#44; H&#41; The expression of BAG3 mRNA in the tumor tissues and normal tissues of&#160;49&#160;BC patients was detected by qRT-PCR&#46; &#40;I&#41; Pearson&#39;s correlation analysis was used to analyze the correlation between BAG3 mRNA expression and miR-135a-5p expression in BC tissues&#46; &#42;<span class="elsevierStyleItalic">p</span> &#60; 0&#46;05&#44; &#42;&#42; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;01&#44; and &#42;&#42;&#42; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;001&#46;</p>"
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          "en" => "<p id="spara004" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">BAG3 reverses the effects of miR-135a-5p on the proliferation&#44; migration&#44; invasion&#44; and cycle of BC cell&#46;</span> &#40;A&#41; miR-NC&#44; miR-mimics&#44; miR mimics&#43;BAG3 and inh-NC&#44; miR-inhibitors&#44; and miR-miR inhibitors&#43;si-BAG3 were co-transfected into MDA-MB-231 and MCF-7 cells&#44; respectively&#44; and the transfection efficiency was detected by qRT-PCR&#46; &#40;B&#41; After transfection&#44; MDA-MB-231 and MCF-7 cells were tested for the viability by CCK-8 assay&#46; &#40;C&#41; After transfection&#44; the proliferation of MDA-MB-231 and MCF-7 cells was detected by BrdU method&#46; &#40;D&#44; E&#41; Changes of the migration and invasion abilities of MDA-MB-231 and MCF-7 cells after transfection were detected by wound healing assay and Transwell assay&#46; &#40;F&#41; Changes of cell cycle of MDA-MB-231 and MCF-7 cells after transfection were detected by flow cytometry&#46; &#42;<span class="elsevierStyleItalic">p</span> &#60; 0&#46;05&#44; &#42;&#42; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;01&#44; and &#42;&#42;&#42; <span class="elsevierStyleItalic">p</span> &#60; 0&#46;001&#46;</p>"
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          "leyenda" => "<p id="spara007" class="elsevierStyleSimplePara elsevierViewall">ER&#44; Estrogen Receptor&#59; PR&#44; Progesterone Receptor&#59; TNM&#44; Tumor&#44; Node&#44; Metastasis staging classification&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t  " align="" valign="top" scope="col">Pathological parameters&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">MiR-135a-5p expression</th><a name="en0004"></a><th class="td" title="\n
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                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">High &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;25&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Low &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0009"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" 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"><a name="en0010"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0013"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;296&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0015"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60; 35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8805; 35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0021"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0025"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Lymphatic metastasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0029"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;013<a class="elsevierStyleCrossRef" href="#tb1fn1"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0035"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ER status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;889&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0045"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0055"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">PR stage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;054&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0061"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0065"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0069"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0070"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">TNM stage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0071"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;004<a class="elsevierStyleCrossRef" href="#tb1fn1"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0075"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8544;&#160;&#43;&#160;&#8545;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0080"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8546;&#160;&#43;&#160;&#8547;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0081"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0085"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Tumor size &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;469&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0090"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8805; 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0091"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0093"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0095"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60; 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0099"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3252690.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tb1fn1"
              "etiqueta" => "a"
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      "titulo" => "References"
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          "identificador" => "cebibsec1"
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            0 => array:3 [
              "identificador" => "bib0001"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A review of clinical aspects of breast cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46; Libson"
                            1 => "M&#46; Lippman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/09540261.2013.852971"
                      "Revista" => array:7 [
                        "tituloSerie" => "Int Rev Psychiatry"
                        "fecha" => "2014"
                        "volumen" => "26"
                        "numero" => "1"
                        "paginaInicial" => "4"
                        "paginaFinal" => "15"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24716497"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0002"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Breast cancer statistics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46; DeSantis"
                            1 => "R&#46; Siegel"
                            2 => "P&#46; Bandi"
                            3 => "A&#46; Jemal"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "CA Cancer J Clin"
                        "fecha" => "2011"
                        "volumen" => "61"
                        "numero" => "6"
                        "paginaInicial" => "409"
                        "paginaFinal" => "418"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0003"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of breast cancer brain metastases&#58; radiotherapy and emerging preclinical approaches"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Mampre"
                            1 => "Y&#46; Mehkri"
                            2 => "S&#46; Rajkumar"
                            3 => "S&#46; Sriram"
                            4 => "J&#46; Hernandez"
                            5 => "B&#46; Lucke-Wold"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.55976/dt.1202216523-36"
                      "Revista" => array:7 [
                        "tituloSerie" => "Diagn Ther"
                        "fecha" => "2022"
                        "volumen" => "1"
                        "numero" => "1"
                        "paginaInicial" => "25"
                        "paginaFinal" => "38"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35782783"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0004"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of breast cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "K&#46;L&#46; Maughan"
                            1 => "M&#46;A&#46; Lutterbie"
                            2 => "P&#46;S&#46; Ham"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am Fam Physician"
                        "fecha" => "2010"
                        "volumen" => "81"
                        "numero" => "11"
                        "paginaInicial" => "1339"
                        "paginaFinal" => "1346"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "MicroRNAs&#58; genomics&#44; biogenesis&#44; mechanism&#44; and function"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "D&#46;P&#46; Bartel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0092-8674(04)00045-5"
                      "Revista" => array:8 [
                        "tituloSerie" => "Cell"
                        "fecha" => "2004"
                        "volumen" => "116"
                        "numero" => "2"
                        "paginaInicial" => "281"
                        "paginaFinal" => "297"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14744438"
                            "web" => "Medline"
                          ]
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                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0006"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Characterization of microRNAs in serum&#58; a novel class of biomarkers for diagnosis of cancer and other diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "X&#46; Chen"
                            1 => "Y&#46; Ba"
                            2 => "L&#46; Ma"
                            3 => "X&#46; Cai"
                            4 => "Y&#46; Yin"
                            5 => "K&#46; Wang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/cr.2008.282"
                      "Revista" => array:7 [
                        "tituloSerie" => "Cell Res"
                        "fecha" => "2008"
                        "volumen" => "18"
                        "numero" => "10"
                        "paginaInicial" => "997"
                        "paginaFinal" => "1006"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18766170"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0007"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Circulating microRNAs as stable blood-based markers for cancer detection"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;S&#46; Mitchell"
                            1 => "R&#46;K&#46; Parkin"
                            2 => "E&#46;M&#46; Kroh"
                            3 => "B&#46;R&#46; Fritz"
                            4 => "S&#46;K&#46; Wyman"
                            5 => "E&#46;L&#46; Pogosova-Agadjanyan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci U S A"
                        "fecha" => "2008"
                        "volumen" => "105"
                        "numero" => "30"
                        "paginaInicial" => "10513"
                        "paginaFinal" => "10518"
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0008"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Effects of miR-135a-5p and miR-141 on proliferation&#44; invasion and apoptosis of colorectal cancer SW620 cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46; Wang"
                            1 => "J&#46; Yang"
                            2 => "H&#46; Zhang"
                            3 => "Y&#46; Liao"
                            4 => "D&#46; Xu"
                            5 => "S&#46; Ma"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Oncol Lett"
                        "fecha" => "2020"
                        "volumen" => "20"
                        "numero" => "1"
                        "paginaInicial" => "914"
                        "paginaFinal" => "920"
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0009"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "miR-135a-5p and miR-124-3p inhibit malignancy of glioblastoma by downregulation of syndecan binding protein"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Lin"
                            1 => "X&#46; Wen"
                            2 => "X&#46; Zhang"
                            3 => "X&#46; Sun"
                            4 => "L&#46; Yunzhi"
                            5 => "R&#46; Peng"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1166/jbn.2018.2579"
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                        "tituloSerie" => "J Biomed Nanotechnol"
                        "fecha" => "2018"
                        "volumen" => "14"
                        "numero" => "7"
                        "paginaInicial" => "1317"
                        "paginaFinal" => "1329"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29944105"
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                          ]
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              "identificador" => "bib0010"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Role of BAG3 in cancer progression&#58; a therapeutic opportunity"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; De Marco"
                            1 => "A&#46; Basile"
                            2 => "V&#46; Iorio"
                            3 => "M&#46; Festa"
                            4 => "A&#46; Falco"
                            5 => "B&#46; Ranieri"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.semcdb.2017.08.049"
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                        "tituloSerie" => "Semin Cell Dev Biol"
                        "fecha" => "2018"
                        "volumen" => "78"
                        "paginaInicial" => "85"
                        "paginaFinal" => "92"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28864347"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0011"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "BAG3 promotes tumour cell proliferation by regulating EGFR signal transduction pathways in triple negative breast cancer"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Shields"
                            1 => "E&#46; Conroy"
                            2 => "T&#46; O&#39;Grady"
                            3 => "A&#46; McGoldrick"
                            4 => "K&#46; Connor"
                            5 => "M&#46;P&#46; Ward"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.18632/oncotarget.24590"
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                        "tituloSerie" => "Oncotarget"
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                        "volumen" => "9"
                        "numero" => "21"
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              "identificador" => "bib0012"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Updates in the treatment of breast cancer with radiotherapy"
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                            0 => "S&#46;A&#46; Castaneda"
                            1 => "J&#46; Strasser"
                          ]
                        ]
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.soc.2017.01.013"
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                        "tituloSerie" => "Surg Oncol Clin N Am"
                        "fecha" => "2017"
                        "volumen" => "26"
                        "numero" => "3"
                        "paginaInicial" => "371"
                        "paginaFinal" => "382"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28576177"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0013"
              "etiqueta" => "13"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gene expression profiling predicts clinical outcome of breast cancer"
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                          "autores" => array:6 [
                            0 => "L&#46;J&#46; van &#39;t Veer"
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                            3 => "Y&#46;D&#46; He"
                            4 => "A&#46;A&#46;M&#46; Hart"
                            5 => "M&#46; Mao"
                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2002"
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                        "numero" => "6871"
                        "paginaInicial" => "530"
                        "paginaFinal" => "536"
                      ]
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                ]
              ]
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            13 => array:3 [
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              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Trends in the development of miRNA bioinformatics tools"
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                          "autores" => array:6 [
                            0 => "L&#46; Chen"
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                            2 => "C&#46; Wang"
                            3 => "Y&#46; Yang"
                            4 => "H&#46; Sun"
                            5 => "G Wong"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/bib/bby054"
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                        "tituloSerie" => "Brief Bioinform"
                        "fecha" => "2019"
                        "volumen" => "20"
                        "numero" => "5"
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                        "paginaFinal" => "1852"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29982332"
                            "web" => "Medline"
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                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0015"
              "etiqueta" => "15"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "MiR-135a-5p represses proliferation of HNSCC by targeting HOXA10"
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                            5 => "X&#46;-&#46;J&#46; Chen"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/15384047.2018.1450112"
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                        "tituloSerie" => "Cancer Biol Ther"
                        "fecha" => "2018"
                        "volumen" => "19"
                        "numero" => "11"
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                        "paginaFinal" => "983"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29580143"
                            "web" => "Medline"
                          ]
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                      ]
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                ]
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                0 => array:2 [
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                      "titulo" => "LncRNA FOXD3-AS1&#47;miR-135a-5p function in nasopharyngeal carcinoma cells"
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                    ]
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                    0 => array:1 [
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                        "tituloSerie" => "Open Med &#40;Wars&#41;"
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            16 => array:3 [
              "identificador" => "bib0017"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Autophagy&#58; renovation of cells and tissues"
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                            0 => "N&#46; Mizushima"
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                    0 => array:2 [
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                        "numero" => "4"
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                        "paginaFinal" => "741"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22078875"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0018"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rapamycin regulates autophagy and cell adhesion in induced pluripotent stem cells"
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                            0 => "A&#46; Sotthibundhu"
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                            3 => "A&#46; Garcia-Munoz"
                            4 => "A&#46; Klawiter"
                            5 => "K&#46; Thompson"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13287-016-0425-x"
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                        "tituloSerie" => "Stem Cell Res Ther"
                        "fecha" => "2016"
                        "volumen" => "7"
                        "numero" => "1"
                        "paginaInicial" => "166"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27846905"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0019"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "BAG3 promotes autophagy and glutaminolysis via stabilizing glutaminase"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Zhao"
                            1 => "J&#46;-&#46;M&#46; Wang"
                            2 => "J&#46; Yan"
                            3 => "D&#46;-L&#46; Zhang"
                            4 => "B&#46;-&#46;Q&#46; Liu"
                            5 => "J&#46;-&#46;Y&#46; Jiang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41419-019-1504-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Death Dis"
                        "fecha" => "2019"
                        "volumen" => "10"
                        "numero" => "4"
                        "paginaInicial" => "284"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30910998"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "At the crossroads of apoptosis and autophagy&#58; multiple roles of the co-chaperone bag3 in stress and therapy resistance of cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46; K&#246;gel"
                            1 => "B&#46; Linder"
                            2 => "A&#46; Brunschweiger"
                            3 => "S&#46; Chines"
                            4 => "C&#46; Behl"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3390/cells9030574"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cells"
                        "fecha" => "2020"
                        "volumen" => "9"
                        "numero" => "3"
                        "paginaInicial" => "574"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32121220"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0021"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2&#8242;-Hydroxycinnamaldehyde induces apoptosis through HSF1-mediated BAG3 expression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "H&#46;A&#46; Nguyen"
                            1 => "S&#46;A&#46; Kim"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Oncol"
                        "fecha" => "2017"
                        "volumen" => "50"
                        "numero" => "1"
                        "paginaInicial" => "283"
                        "paginaFinal" => "289"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0022"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The antiapoptotic protein BAG3 is expressed in thyroid carcinomas and modulates apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Chiappetta"
                            1 => "M&#46; Ammirante"
                            2 => "A&#46; Basile"
                            3 => "A&#46; Rosati"
                            4 => "M&#46; Festa"
                            5 => "M&#46; Monaco"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2006-1712"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Endocrinol Metab"
                        "fecha" => "2007"
                        "volumen" => "92"
                        "numero" => "3"
                        "paginaInicial" => "1159"
                        "paginaFinal" => "1163"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17164298"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0023"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "miR-206 Inhibits Cell Proliferation&#44; Migration&#44; and Invasion by Targeting BAG3 in Human Cervical Cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Y&#46; Wang"
                            1 => "Y&#46; Tian"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Oncol Res"
                        "fecha" => "2018"
                        "volumen" => "26"
                        "numero" => "6"
                        "paginaInicial" => "923"
                        "paginaFinal" => "931"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0024"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Knockdown of BAG3 synergizes with olaparib to kill ovarian cancer cells via repressing autophagy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46; Wang"
                            1 => "J&#46; Zheng"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "J Investig Med"
                        "fecha" => "2020"
                        "volumen" => "69"
                        "numero" => "4"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "BAG3 overexpression and cytoprotective autophagy mediate apoptosis resistance in chemoresistant breast cancer cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;K&#46; Das"
                            1 => "B&#46; Linder"
                            2 => "F&#46; Bonn"
                            3 => "F&#46; Rothweiler"
                            4 => "I&#46; Dikic"
                            5 => "M&#46; Michaelis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.neo.2018.01.001"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neoplasia"
                        "fecha" => "2018"
                        "volumen" => "20"
                        "numero" => "3"
                        "paginaInicial" => "263"
                        "paginaFinal" => "279"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29462756"
                            "web" => "Medline"
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                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
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ISSN: 18075932
Original language: English
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