Journal
ONCOLOGY REPORTS
Volume 31, Issue 1, Pages 397-404Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2013.2831
Keywords
miR-139; hepatocellular carcinoma; T-cell factor-4; beta-catenin
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Funding
- National Natural Science Foundation [81071877]
- Fundamental Research Fund of Xi'an Jiaotong University [2010-01]
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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 3UTR 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 -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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