Hepatitis C virus NS4B protein induces epithelial-mesenchymal transition by upregulation of Snail View Full Text


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Article Info

DATE

2017-04-21

AUTHORS

Bicheng Hu, Shenggao Xie, Yuqian Hu, Wen Chen, Xiaofan Chen, Yi Zheng, Xinxing Wu

ABSTRACT

BackgroundChronic hepatitis C virus (HCV) infection is an important cause of hepatocellular carcinoma (HCC). Epithelial to mesenchymal transition (EMT) is a key process associated with tumor metastasis and poor prognosis. HCV infection, HCV core and NS5A protein could induce EMT process, but the role of NS4B on EMT remains poorly understood.MethodsWe overexpressed HCV NS4B protein in HepG2 cells or Huh7.5.1 cells infected by HCVcc, the E-cadherin expression, N-cadherin expression and the EMT-associated transcriptional factor Snail were determined. The migration and invasion capabilities of the transfected cells were evaluated using wound-healing assay. Additionally, we used Snail siRNA interference to confirm the relation of HCV NS4B and Snail on EMT promotion.ResultsHCV NS4B increased the expression of EMT related markers and promoted cell migration and invasion. Snail knock-down almost completely eliminated the function of NS4B protein in EMT changes and reversed cell migration capacity to lower level. HCV NS4B protein could reduce the expression of Scribble and Hippo signal pathway were subsequently inactivated, resulting in the activation of PI3K/AKT pathway, which may be the reason for the up-regulation of Snail.ConclusionsThis study demonstrates that HCV NS4B protein induces EMT progression via the upregulation of Snail in HCC, which may be a novel underlying mechanism for HCV-associated HCC development, invasion and metastasis. More... »

PAGES

83

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12985-017-0737-1

DOI

http://dx.doi.org/10.1186/s12985-017-0737-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084954587

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28431572


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