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  • Title: Loss-of-function of miR-142 by hypermethylation promotes TGF-β-mediated tumour growth and metastasis in hepatocellular carcinoma.
    Author: Yu Q, Xiang L, Yin L, Liu X, Yang D, Zhou J.
    Journal: Cell Prolif; 2017 Dec; 50(6):. PubMed ID: 28963738.
    Abstract:
    OBJECTIVES: Hypermethylation-induced epigenetic silencing of tumour suppressor genes (TSGs) are frequent events during carcinogenesis. MicroRNA-142 (miR-142) is found to be dysregulated in cancer patients to participate into tumour growth, metastasis and angiogenesis. However, the tumour suppressive role of miR-142 and the status of methylation are not fully understood in hepatocellular carcinoma (HCC). METHODS: Hepatocellular carcinoma tissues and corresponding non-neoplastic tissues were collected. The expression and function of miR-142 and TGF-β in two HCC cell lines were determined. The miRNA-mRNA network of miR-142 was analysed in HCC cell lines. RESULTS: We found that the miR-142 expression was reduced in tumour tissues and two HCC cell lines HepG2 and SMMC7721, which correlated to higher TNM stage, metastasis and differentiation. Moreover, miR-142 was identified to directly target and inhibit transforming growth factor β (TGF-β), leading to decreased cell vitality, proliferation, EMT and the ability of pro-angiogenesis in TGF-β-dependent manner. Interestingly, the status of methylation of miR-142 was analysed and the results found the hypermethylated miR-142 in tumour patients and cell lines. The treatment of methylation inhibitor 5-Aza could restore the expression of miR-142 to suppress the TGF-β expression, which impaired TGF-β-induced tumour growth. CONCLUSION: These findings implicated that miR-142 was a tumour suppressor gene in HCC and often hyermethylated to increase TGF-β-induced development of hepatocellular carcinoma.
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