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

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

doi:10.18632/oncotarget.12144

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Research Papers:

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

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

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Oncotarget. 2016; 7:84575-84586. https://doi.org/10.18632/oncotarget.12144

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Abstract

Beatrice Conti1,*, Cristiana Porcu2,*, Carmela Viscomi1, Antonella Minutolo1,3, Susan Costantini4, Marco Corazzari3, Gino Iannucci1, Barbara Barbaro2, Clara Balsano1,2

1Laboratory of Molecular Virology and Oncoloy, Francesco Balsano Foundation, ex A. Cesalpino Foundation, Rome, Italy

2Institute of Biology and Molecular Pathology (IBPM) – CNR (National Research Council), Rome, Italy

3Department of Biology, University of Rome ‘Tor Vergata’, Rome, Italy

4CROM, Istituto Nazionale Tumori “Fondazione G.Pascale”, IRCSS, Napoli, Italy

*These authors have contributed equally to this work

Correspondence to:

Clara Balsano, email: [email protected]

Keywords: HCV, liver steatosis, SHP1, NS5A, HCC

Received: April 19, 2016 Accepted: August 20, 2016 Published: September 20, 2016

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.

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Research Papers:

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

Abstract