title: Small heterodimer partner 1 directly interacts with NS5A viral protein and has a key role in HCV related liver cell transformation.
abstract: HCV life cycle is strictly correlated with the hepatocyte lipid metabolism; moreover, the progression of HCV chronic hepatitis is accelerated by the presence of liver steatosis. Among the steatogenic genes deregulated during the HCV infection one of the most attractive is the Small Heterodimer Protein 1 (SHP1; NR0B2), that is involved in a remarkable number of metabolic functions. HCV NS5A is an essential and integral component of the HCV membranous-web replicon complex (RC) and plays an essential role to transfer the viral genome from the RCs to the surface of the lipid droplets (LDs) that, in turn, play a key function during HCV life cycle.With the help of a HCV infection model, we demonstrate a functional interaction between SHP1 and HCV NS5A protein. SHP1 silencing (siSHP1) reversed the pro-oncogenic effects of HCV infection, inducing a significant decrease in liver lipid accumulation and in NS5A protein expression. Moreover, siSHP1 causes a strong modulation of some genes involved in HCV-related EMT, such as: HNF4, a central regulators of hepatocyte differentiation, E-Cadherin, SNAILs.Our data suggest that SHP1 results not only to be strictly connected to the pathogenesis of HCV-related liver steatosis, but also to its progression towards the liver transformation.
authors.affiliation: Laboratory of Molecular Virology and Oncoloy, Francesco Balsano Foundation, ex A. Cesalpino Foundation, Rome, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Conti
authors.affiliation: Institute of Biology and Molecular Pathology (IBPM) - CNR (National Research Council), Rome, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Porcu
authors.affiliation: Laboratory of Molecular Virology and Oncoloy, Francesco Balsano Foundation, ex A. Cesalpino Foundation, Rome, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Viscomi
authors.affiliation: Laboratory of Molecular Virology and Oncoloy, Francesco Balsano Foundation, ex A. Cesalpino Foundation, Rome, Italy.|Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Minutolo
authors.affiliation: CROM, Istituto Nazionale Tumori "Fondazione G.Pascale", IRCSS, Napoli, Italy.
authors.forename: Susan
authors.initials: S
authors.lastname: Costantini
authors.affiliation: Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Corazzari
authors.affiliation: Laboratory of Molecular Virology and Oncoloy, Francesco Balsano Foundation, ex A. Cesalpino Foundation, Rome, Italy.
authors.forename: Gino
authors.initials: G
authors.lastname: Iannucci
authors.affiliation: Institute of Biology and Molecular Pathology (IBPM) - CNR (National Research Council), Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Barbaro
authors.affiliation: Laboratory of Molecular Virology and Oncoloy, Francesco Balsano Foundation, ex A. Cesalpino Foundation, Rome, Italy.|Institute of Biology and Molecular Pathology (IBPM) - CNR (National Research Council), Rome, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Balsano
mesh_terms: D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000821:virology; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism / Q000821:virology; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology; D011485:Protein Binding; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D017361:Viral Nonstructural Proteins; C099713:nuclear receptor subfamily 0, group B, member 2; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: HCC; HCV; NS5A; SHP1; liver steatosis