title: Hepatitis C virus represses E-cadherin expression via DNA methylation to induce epithelial to mesenchymal transition in human hepatocytes.
abstract: Hepatitis C virus (HCV) core protein is known to induce promoter hypermethylation of tumor suppressor genes including E-cadherin to repress their expression when overexpressed in human hepatocytes; however, its actual role during HCV infection is still unknown. Here, we report that infection with HCV derived from pJFH-1 replicon system that mimics natural infection elevates protein levels of DNA methyltransferase 1 and 3b to enhance DNMT activity in human hepatocytes. As a consequence, HCV induced promoter hypermethylation of E-cadherin, resulting in repression of its expression. In addition down-regulation of E-cadherin by HCV led to epithelial-mesenchymal transition that is known to be a critical event during the late stage of tumorigenesis.
authors.affiliation: Department of Microbiology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Jungmi
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Microbiology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea. Electronic address: kljang@pusan.ac.kr.
authors.forename: Kyung Lib
authors.initials: KL
authors.lastname: Jang
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D019175:DNA Methylation / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D006801:Humans
chemical_list: D015820:Cadherins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases
keywords: DNA methylation; E-cadherin; Epithelial–mesenchymal transition; Hepatitis C virus