miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway

Gu,Wei; Li,Xiaomei; Wang,Jue

doi:10.3892/or.2013.2831

miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway

Authors:
- Wei Gu
- Xiaomei Li
- Jue Wang
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Affiliations: College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China, Institute of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China
Published online on: November 1, 2013 https://doi.org/10.3892/or.2013.2831
Pages: 397-404

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Abstract

microRNAs (miRNAs) are key post-transcriptional regulators of gene expression in hepatocellular carcinoma (HCC), but their speciﬁc roles and functions have yet to be fully elucidated. In the present study, a significant downregulation of miR-139 expression was demonstrated in HCC samples and HCC cells using quantitative PCR (qPCR). Upregulation of miR-139 in vitro, attenuated HCC cell growth, migration/invasion and induced apoptosis. Based on computational and expression analysis, we noted that miR-139 can control the expression of T-cell factor-4 (TCF-4) as a target gene. A reporter assay with the 3'UTR of TCF-4 cloned downstream of a luciferase gene showed decreased luciferase activity in the presence of miR-139, providing strong evidence that miR-139 is a direct regulator of TCF-4. Furthermore, we observed that restoration of TCF-4 activity resulted in effects that were similar to those following transfection of the miR-139 inhibitor into HCC cells. Finally, mechanistic investigation revealed that the overexpression of miR-139 suppressed the β-catenin/TCF-4 transcriptional activity by targeting TCF-4. In conclusion, our study demonstrates that miR-139 downregulation is common in HCC and that overexpression of miR-139 expression inhibits cell proliferation and invasion, suggesting that miR-139 may provide a therapeutic strategy for the treatment of HCC patients.

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