Qiangfeng Yu1,2, Leyang Xiang1, Libo Yin3, Xincheng Liu4, Dinghua Yang1, Jianyin Zhou5. 1. Department of Hepatobiliary Surgery, Nanfang Hospital Affiliated to Southern Medical University, Guangzhou, China. 2. Department of Hepatobiliary Surgery, The Second Hospital of Longyan, Longyan, China. 3. Department of Hepatobiliary Surgery, Changzhou No. 2 People's Hospital, Nanjing Medical University, Changzhou, Jiangsu, China. 4. The Second Affiliated Hospital of Shantou University Medical College, Shantou, China. 5. Department of Hepatobiliary and Pancreatic Surgery, Zhongshan Hospital, Xiamen University, Xiamen, China.
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.
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 cancerpatients 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 tumourpatients 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.
Authors: Juan Sandoval; Angel Díaz-Lagares; Rocío Salgado; Octavio Servitje; Fina Climent; Pablo L Ortiz-Romero; Amparo Pérez-Ferriols; Maria P Garcia-Muret; Teresa Estrach; Mar Garcia; Lara Nonell; Manel Esteller; Ramon M Pujol; Blanca Espinet; Fernando Gallardo Journal: J Invest Dermatol Date: 2014-11-18 Impact factor: 8.551
Authors: Shiqi Zhang; Tao Zeng; Bin Hu; Yu-Hang Zhang; Kaiyan Feng; Lei Chen; Zhibin Niu; Jianhao Li; Tao Huang; Yu-Dong Cai Journal: Front Bioeng Biotechnol Date: 2020-05-26