miR-1 and miR-145 act as tumor suppressor microRNAs in gallbladder cancer

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dc.contributor.authorLetelier, Pablo
dc.contributor.authorGarcia, Patricia
dc.contributor.authorLeal, Pamela
dc.contributor.authorAlvarez, Hector
dc.contributor.authorIli, Carmen
dc.contributor.authorLopez, Jaime
dc.contributor.authorCastillo, Jonathan
dc.contributor.authorBrebi, Priscilla
dc.contributor.authorRoa, Juan Carlos
dc.date2014
dc.date.accessioned2021-04-30T17:04:10Z
dc.date.available2021-04-30T17:04:10Z
dc.description.abstractThe development of miRNA-based therapeutics represents a new strategy in cancer treatment. The objectives of this study were to evaluate the differential expression of microRNAs in gallbladder cancer (GBC) and to assess the functional role of miR-1 and miR-145 in GBC cell behavior. A profile of miRNA expression was determined using Dharmacon (TM) microarray technology. Differential expression of five microRNAs was validated by TaqMan reverse transcription quantitative-PCR in a separate cohort of 8 tumors and 3 non-cancerous samples. Then, we explored the functional role of miR-1 and miR-145 in tumor cell behavior by ectopic in vitro expression in the GBC NOZ cell line. Several miRNAs were found to be aberrantly expressed in GBC; most of these showed a significantly decreased expression compared to non-neoplastic tissues (Q value < 0.05). The differential expression of 7 selected miRNAs was confirmed by real time PCR. Pathway enrichment analysis revealed that the most deregulated miRNAs (miR-1, miR-133, miR-143 and miR-145) collectively targeted a number of genes belonging to signaling pathways such as TGF-beta, ErbB3, WNT and VEGF, and those regulating cell motility or adhesion. The ectopic expression of miR-1 and miR-145 in NOZ cells significantly inhibited cell viability and colony formation (P < 0.01) and reduced gene expression of VEGF-A and AXL. This study represents the first investigation of the miRNA expression profile in gallbladder cancer, and our findings showed that several miRNAs are deregulated in this neoplasm. In vitro functional assays suggest that miR-1 and miR-145 act as tumor suppressor microRNAs in GBC.
dc.identifier.citationINTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY,Vol.7,1849-1867,2014
dc.identifier.urihttp://repositoriodigital.uct.cl/handle/10925/3858
dc.language.isoen
dc.publisherE-CENTURY PUBLISHING CORP
dc.sourceINTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY
dc.subject.englishGallbladder cancer
dc.subject.englishmicroRNAs
dc.subject.englishmiR-1
dc.subject.englishmiR-145
dc.subject.englishNOZ cells
dc.titlemiR-1 and miR-145 act as tumor suppressor microRNAs in gallbladder cancer
dc.typeArticle
uct.catalogadorWOS
uct.indizacionSCI
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