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Hepatitis C virus core protein exerts an inhibitory effect on suppressor of cytokine signaling (SOCS)-1 gene expression.

Abstract：

BACKGROUND/AIMS:Suppressor of cytokine signaling (SOCS)-1, a negative feedback regulator of cytokine signaling pathway, also has a tumor suppressor activity, the silencing of its gene by hypermethylation is suggested to contribute to hepatocarcinogenesis. We studied the effect of the core protein of hepatitis C virus (HCV) on the expression of SOCS-1 gene. METHODS:HCV core gene transgenic mice, which develop hepatocellular carcinoma late in life, HepG2 cells expressing the core protein, and human liver tissues were analyzed. RESULTS:The expression of SOCS-1 gene was significantly suppressed in the liver of core gene transgenic mice and HepG2 cells expressing the core protein, while that of SOCS-3 gene was conserved. SOCS-1 expression levels also decreased in HCV-positive human liver tissues. The core protein differentially down-regulated the expression of signal transducer and activator of transcription (STAT) target genes, but rather enhanced STAT1 and STAT3 activation after interleukin-6 stimulation in mouse liver tissues and cells. CONCLUSIONS:HCV core protein down-regulates the expression of SOCS-1 gene. This is a mechanism leading to SOCS-1 silencing, an alternative to the hypermethylation of the gene; this effect of the core protein may modulate the intracellular signaling pathway, contributing to the pathogenesis in HCV infection including hepatocarcinogenesis.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Miyoshi H,Fujie H,Shintani Y,Tsutsumi T,Shinzawa S,Makuuchi M,Kokudo N,Matsuura Y,Suzuki T,Miyamura T,Moriya K,Koike K

doi

10.1016/j.jhep.2005.03.028

subject

Has Abstract

pub_date

2005-11-01 00:00:00

pages

757-63

issue

5

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(05)00322-3

journal_volume

43

pub_type

杂志文章

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