Wnt/β-Catenin activates MiR-183/96/182 expression in hepatocellular carcinoma that promotes cell invasion
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AbstractNearly 50% of known miRNAs are found in clusters and transcribed as polycistronic transcripts. In this study, we showed that over-expression of miR-183/96/182 cluster is frequent in hepatocellular carcinoma (HCC), a highly aggressive malignancy that is commonly fatal. In a cohort of HCC patients (n = 81), miR-183/96/182 up-regulation correlated with metastatic features including presence of microvascular invasion, advanced tumor differentiation, and shorter recurrence-free survival. Univariate and multivariate analyses further showed miR-183/96/182 over-expression represented an independent prognostic factor (Relative Risk: 2.0471; P = 0.0289). Functional investigation using siRNA against miR-183/96/182 in two invasive HCC cells indicated significant inhibition on cell migration and invasion without affecting cell viability. Forkhead boxO1 (FOXO1) was further validated as a downstream target of these three miRNAs. In investigating the regulatory mechanism underlining miR-183/96/182 over-expression, a direct interaction of CTNNB1 on the promoter region was confirmed by ChIP-PCR and luciferase reporter validations. Knockdown of CTNNB1 also showed concordant down-regulations of miR-183, -96 and -182, and the re-expression of FOXO1. Our findings demonstrated that over-expression of miR-183/96/182 confers an oncogenic function in HCC cell dissemination, and could serve as an independent prognostic predictor for HCC patients.
All Author(s) ListLeung W.K.C., He M., Chan A.W.H., Law P.T.Y., Wong N.
Journal nameCancer Letters
Year2015
Month1
Day1
Volume Number362
Issue Number1
PublisherElsevier BV
Place of PublicationNetherlands
Pages97 - 105
ISSN0304-3835
eISSN1872-7980
LanguagesEnglish-United Kingdom
KeywordsHepatocellular carcinoma, MiR-182, MiR-183, MiR-96

Last updated on 2020-27-10 at 02:59