title: Epigenetic regulation of miR-124 by hepatitis C virus core protein promotes migration and invasion of intrahepatic cholangiocarcinoma cells by targeting SMYD3.
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.
authors: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
authors: Bing
authors: B
authors: Zeng
authors: Zhihua
authors: Z
authors: Li
authors: Rufu
authors: R
authors: Chen
authors: Ning
authors: N
authors: Guo
authors: Jiajia
authors: J
authors: Zhou
authors: Quanbo
authors: Q
authors: Zhou
authors: Qing
authors: Q
authors: Lin
authors: Di
authors: D
authors: Cheng
authors: Qiaofang
authors: Q
authors: Liao
authors: Liping
authors: L
authors: Zheng
authors: Yuanfeng
authors: Y
authors: Gong
mesh_terms: D001483:Base Sequence; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D002465:Cell Movement; D018281:Cholangiocarcinoma / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D055785:Gene Knockdown Techniques; D016174:Hepacivirus / Q000472:pathogenicity* / Q000502:physiology; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014758:Viral Core Proteins / Q000502:physiology*
chemical_list: C509207:MIRN124 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D014758:Viral Core Proteins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D011495:Histone-Lysine N-Methyltransferase; C506278:SMYD3 protein, human; D020780:Matrix Metalloproteinase 9