title: Anti-apoptotic effect of HCV core gene of genotype 3a in Huh-7 cell line.
abstract: BACKGROUND
  Hepatitis C virus (HCV) Core protein regulates multiple signaling pathways and alters cellular genes expression responsible for HCV induced pathogenesis leading to hepatocellular carcinoma (HCC). Prevalence of HCV genotype 3a associated HCC is higher in Pakistan as compare to the rest of world; however the molecular mechanism behind this is still unclear. This study has been designed to evaluate the effect of HCV core 3a on apoptosis and cell proliferation which are involved in HCC METHODOLOGY: We examined the in vitro effect of HCV Core protein of genotype 3a and 1a on cellular genes involved in apoptosis by Real time PCR in liver cell line (Huh-7). We analyzed the effect of HCV core of genotype 1a and 3a on cell proliferation by MTT assay and on phosphrylation of Akt by western blotting in Huh-7 cells.
  
  
  RESULTS
  The HCV 3a Core down regulates the gene expression of Caspases (3, 8, 9 and 10), Cyto C and p53 which are involved in apoptosis. Moreover, HCV 3a Core gene showed stronger effect in regulating protein level of p-Akt as compared to HCV 1a Core accompanied by enhanced cell proliferation in Huh-7 cell line.
  
  
  CONCLUSIONS
  From the current study it has been concluded that reduced expression of cellular genes involved in apoptosis, increased p-Akt (cell survival gene) and enhanced cell proliferation in response to HCV 3a core confirms anti apoptotic effect of HCV 3a Core gene in Huh-7 that may lead to HCC.
authors: Centre of Excellence in Molecular Biology, University of the Punjab, Pakistan. captainmalik@hotmail.com
authors: Shah
authors: S
authors: Jahan
authors: Saba
authors: S
authors: Khaliq
authors: Muhammad Hassan
authors: MH
authors: Siddiqi
authors: Bushra
authors: B
authors: Ijaz
authors: Waqar
authors: W
authors: Ahmad
authors: Usman A
authors: UA
authors: Ashfaq
authors: Sajida
authors: S
authors: Hassan
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D020869:Gene Expression Profiling; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010154:Pakistan; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D060888:Real-Time Polymerase Chain Reaction; D013194:Staining and Labeling / Q000379:methods; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014758:Viral Core Proteins / Q000378:metabolism*
chemical_list: D013778:Tetrazolium Salts; D013844:Thiazoles; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D051058:Oncogene Protein v-akt; C022616:thiazolyl blue