Journal
FEBS LETTERS
Volume 586, Issue 19, Pages 3271-3278Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2012.06.049
Keywords
miR-124; Hepatitis C Virus core protein; DNMT1; SMYD3; Intrahepatic cholangiocarcinoma
Funding
- National Natural Science Foundation of China [30872485]
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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. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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