Epigenetic regulation of miR-124 by Hepatitis C Virus core protein promotes migration and invasion of intrahepatic cholangiocarcinoma cells by targeting SMYD3

• Published in: FEBS letters Vol. 586; no. 19; pp. 3271 - 3278
• Main Authors: Zeng, Bing, Li, Zhihua, Chen, Rufu, Guo, Ning, Zhou, Jiajia, Zhou, Quanbo, Lin, Qing, Cheng, Di, Liao, Qiaofang, Zheng, Liping, Gong, Yuanfeng
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 21.09.2012
• Subjects: Base Sequence; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cell Line, Tumor; Cell Movement; Cholangiocarcinoma - genetics; Cholangiocarcinoma - pathology; Cholangiocarcinoma - physiopathology; Cholangiocarcinoma - virology; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases - metabolism; DNA methyltransferase; DNMT; DNMT1; Down-Regulation; Epigenesis, Genetic; Gene Knockdown Techniques; HCVc; Hepacivirus - pathogenicity; Hepacivirus - physiology; Hepatitis C virus; Hepatitis C Virus core protein; Histone-Lysine N-Methyltransferase - antagonists & inhibitors; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; Humans; ICC; Intrahepatic cholangiocarcinoma; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Liver Neoplasms - physiopathology; Liver Neoplasms - virology; Matrix Metalloproteinase 9 - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; miR-124; Neoplasm Invasiveness; Proto-Oncogene Proteins c-myc - metabolism; SET and MYND domain-containing protein 3; SMYD3; Viral Core Proteins - physiology; miR-124; DNMT; Hepatitis C Virus core protein; DNMT1; Intrahepatic cholangiocarcinoma; ICC; HCVc; SMYD3
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2012.06.049

► MiR-124 is down-regulated in HCV-ICC. ► The induction of DNMT1 by HCVc mediated the suppression of miR-124. ► Low miR-124 expression level promotes cell migration and invasion by targeting SMYD3. ► Our study casts a new light on the functions of miR-124 as both genetic and epigenetic regulators. Hepatitis C Virus core protein (HCVc) plays important roles in the development of intrahepatic cholangiocarcinoma (ICC). MicroRNAs (miRNAs) contribute to tumor progression by interacting with downstream target genes. However, the regulation and role of miRNAs in HCV-related intrahepatic cholangiocarcinoma (HCV-ICC) is poorly understood. In this study, we found that miR-124 was down-regulated in HCV-ICC and the induction of DNMT1 by HCVc mediated the suppression of miR-124. Over-expression of miR-124 suppressed cell migration and invasion in vitro, and reduced the protein levels of SMYD3 and downstream target genes (c-Myc and MMP9). Knockdown of SMYD3 inhibited cell migration and invasion resembling that of miR-124 over-expression. In conclusion, our studies indicate that low miR-124 levels mediated by HCVc via DNMT1 promote ICC cell migration and invasion by targeting SMYD3.