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World J Gastroenterol. Jan 7, 2019; 25(1): 42-58
Published online Jan 7, 2019. doi: 10.3748/wjg.v25.i1.42
Hepatitis C virus core protein modulates several signaling pathways involved in hepatocellular carcinoma
Shahab Mahmoudvand, Somayeh Shokri, Reza Taherkhani, Fatemeh Farshadpour
Shahab Mahmoudvand, Somayeh Shokri, Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 6135715794, Iran
Shahab Mahmoudvand, Somayeh Shokri, Department of Medical Virology, School of Medicine, Hamadan University of Medical Sciences, Hamadan 6517838736, Iran
Reza Taherkhani, Fatemeh Farshadpour, The Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran
Author contributions: Mahmoudvand S designed the research and wrote the paper; Shokri S provided the literature review and wrote the paper; Taherkhani R performed research and contributed to writing the paper; Farshadpour F designed the study, edited the manuscript and was involved in writing the paper.
Conflict-of-interest statement: The authors declare that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Fatemeh Farshadpour, PhD, Associate Professor, The Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Moallem Street, Bushehr 7514633341, Iran. f.farshadpour@bpums.ac.ir
Telephone: +98-9171712653
Received: October 19, 2018
Peer-review started: October 19, 2018
First decision: November 29, 2018
Revised: December 7, 2018
Accepted: December 13, 2018
Article in press: December 13, 2018
Published online: January 7, 2019
Processing time: 80 Days and 15 Hours
Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer, and hepatitis C virus (HCV) infection plays a major role in HCC development. The molecular mechanisms by which HCV infection leads to HCC are varied. HCV core protein is an important risk factor in HCV-associated liver pathogenesis and can modulate several signaling pathways involved in cell cycle regulation, cell growth promotion, cell proliferation, apoptosis, oxidative stress and lipid metabolism. The dysregulation of signaling pathways such as transforming growth factor β (TGF-β), vascular endothelial growth factor (VEGF), Wnt/β-catenin (WNT), cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor α (PPARα) by HCV core protein is implicated in the development of HCC. Therefore, it has been suggested that this protein be considered a favorable target for further studies in the development of HCC. In addition, considering the axial role of these signaling pathways in HCC, they are considered druggable targets for cancer therapy. Therefore, using strategies to limit the dysregulation effects of core protein on these signaling pathways seems necessary to prevent HCV-related HCC.

Keywords: Hepatitis C virus; Core protein; Transforming growth factor β; Vascular endothelial growth factor; Wnt/β-catenin; Cyclooxygenase-2; Peroxisome proliferator-activated receptor α; Hepatocellular carcinoma

Core tip: Hepatitis C virus (HCV) core protein can modulate several signaling pathways involved in cell cycle regulation, cell growth promotion, cell proliferation, apoptosis, oxidative stress and lipid metabolism. The dysregulation of these signaling pathways by HCV core protein is implicated in the development of hepatocellular carcinoma (HCC). Considering the axial role of these signaling pathways in HCC, they are considered druggable targets for cancer therapy. Therefore, using strategies to limit the dysregulation effects of core protein on these signaling pathways seems necessary to prevent HCV-related HCC.