Hepatitis C virus Core protein stimulates cell growth by down-regulating p16 expression via DNA methylation

Hepatitis C virus core protein inhibits E6AP expression via DNA methylation to escape from ubiquitin-dependent proteasomal degradation

“…The present study took advantage of the HCV replication system to demonstrate that HCV core protein activates DNMT by elevating DNMT1 and 3b levels. In addition, the present study suggests that HCV core protein stimulates DNMT1 expression via upregulation of AP-1 activity, as previously demonstrated with HCV core overexpression systems [29]. Our study also showed that HCV core protein inhibits E6AP expression via promoter hypermethylation.…”

“…2A). According to previous reports, HCV core protein enhances AP-1 transcriptional activity and thereby activates the DNMT1 promoter that contains the binding motifs of the AP-1 complex [29]. Consistently, HCV infection induced the phosphorylation of c-Jun without affecting its protein levels and significantly increased the DNMT promoter activity (Fig.…”

“…For transient expression, 2 × 10 5 cells per 60-mm dish were transfected with 1 μg of the appropriate plasmid(s) using WelFect-EX™ PLUS (WelGENE) following the manufacturer's instructions. Stable cell lines, HepG2-vector and HepG2-Core, were established by transfection with pCMV-3 × HA1 and pCMV-3 × HA1-Core, respectively, followed by selection with 500 μg/ml G418 (Gibco) [29]. For the luciferase assay, E6AP-luc was cotransfected with either an empty vector or an effector plasmid under the indicated conditions.…”

Aberrant Methylation of Promoter Region of SPINT2/HAI-2 Gene: An Epigenetic Mechanism in Hepatitis C Virus-Induced Hepatocarcinogenesis

“…The higher frequency of aberrant methylation of SPINT2/ HAI-2 gene promoter noted in our cirrhotic cases compared to the control group could be explained by persistent HCVinduced inflammation or generation of reactive oxygen species (Nishida 2010), although studies suggest a direct role of HCV in epigenetic regulations (Guo et al, 2011;Park et al, 2011;Ripoli et al, 2011). The association between hepatitis virus and hypermethylation was supported by Saito et al (2001), who observed a higher frequency of CpG island methylation in hepatitis virus-positive HCC than in hepatitis virus-negative ones.…”

Epigenetic Mechanisms in Hepatitis C Virus-Associated Hepatocellular Carcinoma: A Potential New Link Between Stem Cells, Virology and Cancer

“…More recent studies suggest that HCV viral genes might be directly involved in epigenetic regulation. For example, HCV core protein from HCV genotype 1b can inhibit CDKN2A (p16) expression by inducing promoter methylation via up regulation of DNMT1 and DNMT3b in HepG2 cells (Park et al, 2011), while HCV core protein induces CDH1 methylation thus reducing its expression via up regulation of SIRT1 in Huh7 cells (Ripoli et al, 2011). Similarly, it has also been shown that HCV core protein induces RASSF1A promoter methylation through upregulatingexpression of SET and MYND domain containing 3 (SMYD3), a novel histone methyltransferase, in cholangiocarcinoma cells (Guo et al, 2011).…”