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Article

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

  • Authors:
    • Wei Gu
    • Xiaomei Li
    • Jue Wang
  • View Affiliations / Copyright

    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
  • Pages: 397-404
    |
    Published online on: November 1, 2013
       https://doi.org/10.3892/or.2013.2831
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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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Copy and paste a formatted citation
Spandidos Publications style
Gu W, Li X and Wang J: miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway. Oncol Rep 31: 397-404, 2014.
APA
Gu, W., Li, X., & Wang, J. (2014). miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway. Oncology Reports, 31, 397-404. https://doi.org/10.3892/or.2013.2831
MLA
Gu, W., Li, X., Wang, J."miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway". Oncology Reports 31.1 (2014): 397-404.
Chicago
Gu, W., Li, X., Wang, J."miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway". Oncology Reports 31, no. 1 (2014): 397-404. https://doi.org/10.3892/or.2013.2831
Copy and paste a formatted citation
x
Spandidos Publications style
Gu W, Li X and Wang J: miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway. Oncol Rep 31: 397-404, 2014.
APA
Gu, W., Li, X., & Wang, J. (2014). miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway. Oncology Reports, 31, 397-404. https://doi.org/10.3892/or.2013.2831
MLA
Gu, W., Li, X., Wang, J."miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway". Oncology Reports 31.1 (2014): 397-404.
Chicago
Gu, W., Li, X., Wang, J."miR-139 regulates the proliferation and invasion of hepatocellular carcinoma through the WNT/TCF-4 pathway". Oncology Reports 31, no. 1 (2014): 397-404. https://doi.org/10.3892/or.2013.2831
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