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, Gino Iannucci, Barbara Barbaro, Clara Balsano

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)84575-84586
Number of pages12
JournalOncotarget
Volume7
Issue number51
DOIs
Publication statusPublished - 2016

Keywords

  • HCC
  • HCV
  • Liver steatosis
  • NS5A
  • SHP1

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'Small heterodimer partner 1 directly interacts with NS5A viral protein and has a key role in HCV related liver cell transformation'. Together they form a unique fingerprint.

Cite this