Journal
LIVER INTERNATIONAL
Volume 32, Issue 5, Pages 752-760Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1478-3231.2011.02750.x
Keywords
hepatocellular carcinoma; microRNA-122; T-cell factor-4; Wnt signalling; ss-catenin
Categories
Funding
- National High-tech and Program (863 Program) [2008AA 02Z109]
- Zhejiang Provincial Natural Science Foundation of China [Y2080304]
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Aims: To validate whether the anti-cancer effect of microRNA-122 (miR-122) on hepatocellular carcinoma (HCC) is mediated through regulating Wnt/ b-catenin signalling pathways. Methods: The expression levels of miR-122 in HCC tissues and varied hepatoma cells were quantified by real-time PCR. MiR-122 agomir was transfected into HepG2, Hep3B cells to over-express miR-122. The effect of over-expression miR-122 on proliferation and apoptosis of HepG2 and Hep3B cells was evaluated using CCK-8 kit and flow cytometer respectively. The 3'-UTR segments of Wnt1 containing the miR-122 binding sites were amplified by PCR and the luciferase activity in the transfected cells was assayed. Wnt1 mRNA level was quantified using RT-PCR. Protein levels of Wnt1, b-catenin and TCF-4 were detected using Western blotting. Results: In comparison with the expression level of miR-122 in para-cancerous tissues or Chang liver cell, the expression level in HCC tissues or varied hepatoma cells was significantly decreased (P < 0.05). Over-expression of miR-122 significantly inhibited the proliferation (P < 0.05), and promoted the apoptosis of HepG2 and Hep3B cells. Over-expressed miR-122 down-regulated the protein levels of Wnt1, b-catenin and TCF-4 (P < 0.05). MiR-122 suppressed the luciferase activity of the pmiR-Wnt1-wt by approximately 50% compared with the negative control, while mutation or removal of the miR-122 binding site using siRNA or mir-122 inhibitor blocked the suppressive effect (P < 0.05). Conclusions: MiR-122 expression is down-regulated in human HCC. Overexpression of miR-122 inhibits HCC cell growth and promotes the cell apoptosis by affecting Wnt/ b-catenin-TCF signalling pathway.
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