title: DNA methyltransferases 1 and 3b expression in Huh-7 cells expressing HCV core protein of different genotypes.
abstract: BACKGROUND
  Hepatitis C virus infects ~3% of the population and it is a risk factor for hepatocarcinogenesis. The epigenetic mechanisms of HCV-induced hepatocyte transformation towards malignancy in this context are unclear.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the effect of HCV core proteins of different genotypes on DNA methyltransferases (DNMTs) induction.
  
  
  METHODS
  We investigated DNMT1, DNMT3b and E-Cadherin (CDH1) mRNA and protein expression levels in an in vitro model of Huh-7 cells expressing the HCV core protein of different genotypes: 1b, 2a, 3a, 4h and 5a.
  
  
  RESULTS
  We found that both mRNA and protein expression levels of DNMT1 and 3b were upregulated in genotype 1b HCV core expressing cells as compared to control cells. DNMT3b mRNA levels did not change in genotypes 2a, 3a, 4h and 5a, but were upregulated at the protein level by genotype 1b, 2a, 3a. CDH1 mRNA expression was downregulated only in genotype 1b, whereas its protein expression resulted in downregulation by the HCV core of genotypes 1b, 2a and 3a. Conversely, no significant changes were observed for DNMTs and CDH1 investigated in Huh-7 cells expressing the genotypes 4h and 5a. Furthermore, we present evidence that HCV core 1b protein expression induces DNMTs overexpression through STAT3 protein as demonstrated by NSC74859 treatment. Moreover, SIRT1 inhibition affected DNMT1 and 3b expression only in HCV core protein genotype 1b expressing cells as demonstrated by treatment with its inhibitor sirtinol.
  
  
  CONCLUSIONS
  Our findings suggest that HCV core protein could play a role in HCC development at least in part by altering DNMTs expression.
authors.affiliation: Gastroenterology Unit , I.R.C.C.S Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Foggia, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Benegiamo
authors.forename: Manlio
authors.initials: M
authors.lastname: Vinciguerra
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Mazzoccoli
authors.forename: Ada
authors.initials: A
authors.lastname: Piepoli
authors.forename: Angelo
authors.initials: A
authors.lastname: Andriulli
authors.forename: Valerio
authors.initials: V
authors.lastname: Pazienza
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002417:Cattle; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D009284:Naphthols / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014758:Viral Core Proteins / Q000235:genetics*; D000097584:DNA Methyltransferase 3B
chemical_list: D001549:Benzamides; D015820:Cadherins; D004248:DNA (Cytosine-5-)-Methyltransferases; D009284:Naphthols; D012333:RNA, Messenger; D012097:Repressor Proteins; D014758:Viral Core Proteins; D000097584:DNA Methyltransferase 3B; C411744:DMAP1 protein, human; C069130:nucleocapsid protein, Hepatitis C virus; C439060:sirtinol