Small heterodimer partner 1 directly interacts with NS5A viral protein and has a key role in HCV related liver cell transformation.

Beatrice Conti,Susan Costantini,Barbara Barbaro,Marco Corazzari,Clara Balsano,Antonella Minutolo,Carmela Viscomi,Cristiana Porcu,Gino Iannucci

doi:10.18632/oncotarget.12144

Beatrice Conti, Susan Costantini + Show 7 more

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https://doi.org/10.18632/oncotarget.12144

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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.

Highlights

The hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide [1]
HCV life cycle is strictly correlated with the hepatocyte lipid metabolism; the progression of HCV chronic hepatitis is accelerated by the presence of liver steatosis
Our previously published data indicated that HCV infected patients were characterized by a deep deregulation of some genes involved in the control of lipid metabolism

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Introduction

The hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide [1]. An interesting aspect of the HCV life cycle is its strict correlation with the hepatocyte lipid metabolism. With lipoproteins, lipid droplets and host cofactors, favors HCV replication, morphogenesis, and secretion [3, 4]. HCV replication, virion assembly and release, perturb lipid metabolism of infected hepatocytes [5, 6]. NS5A viral protein plays an essential role in transferring the viral genome from the RCs to the surface of the lipid droplets [7]

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