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Acta Pharmacol Sin ; 35(9): 1207-14, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25087998

RESUMO

AIM: MiR-506 is a miRNA involved in carcinogenesis of several kinds of cancer. In this study, we explored whether miR-506 played a critical role in hepatocellular carcinoma (HCC). METHODS: Twenty HCC and adjacent normal liver tissue samples were collected. Human hepatoma cell lines HepG2 and H7402 were used for in vitro studies. The expression of miR-506 and transcriptional co-activator YAP was examined using qRT-PCR. Western blot analysis was used to measure the expression of YAP and its target genes. Luciferase reporter gene assay was used to identify YAP as a target gene of miR-506. MTT and EdU assays were carried out for functional analysis. RESULTS: The expression of miR-506 was significantly lower in HCC than in adjacent normal liver tissues. Bioinformatics analysis revealed that YAP mRNA might be one of the targets of miR-506, and miR-506 in HCC tissues was found to be negatively correlated with YAP (r=-0.605). In both HepG2 and H7402 cells, miR-506 dose-dependently down-regulated YAP and its target genes c-Myc and the connective tissue growth factor (CTGF). Luciferase reporter gene assays demonstrated that miR-506 targeted the wild type 3'UTR of YAP mRNA, but not a 3'UTR with a mutant seed site. Furthermore, miR-506 significantly inhibited the proliferation of HepG2 and H7402 cells, while anti-miR-506 enhanced the cell proliferation, which was blocked by YAP siRNA. CONCLUSION: MiR-506 suppresses the proliferation of hepatoma cells by targeting YAP mRNA.


Assuntos
Regiões 3' não Traduzidas/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma Hepatocelular/genética , Proliferação de Células/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Fosfoproteínas/genética , RNA Mensageiro/genética , Linhagem Celular Tumoral , Células Hep G2 , Humanos , Fatores de Transcrição , Proteínas de Sinalização YAP
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