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

Bing Zeng; Zhihua Li; Rufu Chen; Ning Guo; Jiajia Zhou; Quanbo Zhou; Qing Lin; Di Cheng; Qiaofang Liao; Liping Zheng; Yuanfeng Gong

doi:10.1016/j.febslet.2012.06.049

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

FEBS Lett. 2012 Sep 21;586(19):3271-8. doi: 10.1016/j.febslet.2012.06.049. Epub 2012 Jul 20.

Authors

Bing Zeng¹, Zhihua Li, Rufu Chen, Ning Guo, Jiajia Zhou, Quanbo Zhou, Qing Lin, Di Cheng, Qiaofang Liao, Liping Zheng, Yuanfeng Gong

Affiliation

¹ Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.

PMID: 22819820
DOI: 10.1016/j.febslet.2012.06.049

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
Down-Regulation
Epigenesis, Genetic
Gene Knockdown Techniques
Hepacivirus / pathogenicity*
Hepacivirus / physiology
Histone-Lysine N-Methyltransferase / antagonists & inhibitors
Histone-Lysine N-Methyltransferase / genetics
Histone-Lysine N-Methyltransferase / metabolism*
Humans
Liver Neoplasms / genetics
Liver Neoplasms / pathology
Liver Neoplasms / physiopathology
Liver Neoplasms / virology*
Matrix Metalloproteinase 9 / metabolism
MicroRNAs / genetics*
MicroRNAs / metabolism*
Neoplasm Invasiveness
Proto-Oncogene Proteins c-myc / metabolism
Viral Core Proteins / physiology*

Substances

MIRN124 microRNA, human
MYC protein, human
MicroRNAs
Proto-Oncogene Proteins c-myc
Viral Core Proteins
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases
DNMT1 protein, human
Histone-Lysine N-Methyltransferase
SMYD3 protein, human
Matrix Metalloproteinase 9