Loss‐of‐function of miR‐142 by hypermethylation promotes TGF ‐β‐mediated tumour growth and metastasis in hepatocellular carcinoma

作者：Qiangfeng Yu, Leyang Xiang, Libo Yin, Xincheng Liu, Dinghua Yang, Jianyin Zhou · 发表于：Cell Proliferation · 年份：2017 · DOI：10.1111/cpr.12384 · 被引用次数：48 · 研究领域：MicroRNA in disease regulation、Kruppel-like factors research、TGF-β signaling in diseases

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 inc...