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miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway.
|Title||miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Gu W, Li X, Wang J|
|Date Published||2014 Jan|
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.
|Alternate Journal||Oncol. Rep.|