Hepatitis C virus core protein modulates pRb2/p130 expression in human hepatocellular carcinoma cell lines through promoter methylation

摘要: Hepatitis C Virus (HCV) infection is associated with chronically evolving disease and development of hepatocellular carcinoma (HCC), albeit the mechanism HCC induction by HCV still controversial. The nucleocapsid (core) protein has been shown to be directly implicated in cellular transformation immortalization, enhancing effect oncogenes decreasing one tumor suppressor genes, as RB1 its product pRB. With aim identifying novel molecular mechanisms hepatocyte HCV, we examined core on expression whole Retinoblastoma (RB) family growth factors, i.e. pRb, p107 pRb2/p130. We used a model system consisting HuH-7, HCV-free, human cell line HuH-7-CORE cells derived from former constitutively expressing protein. determined pRb2/p130 mRNA amount respective genes RB1, RBL1 RBL2, RBL2 promoter activity methylation well DNA methyltransferase 1 (DNMT1) 3b (DNMT3b) level. over-expression core-expressing was also evaluated. found that down-regulated levels inducing hyper-methylation concomitant up-regulation DNMT1 DNMT3b expression. When artificially re-established cells, cycle analysis outlined an accumulation G0/G1 phase, expected. appears indeed able significantly down-regulate function two out three RB pRb functional consequences at level regulation, possibly more complex homeostatic processes, may represent plausible involved liver HCV.