Hepatitis C virus core protein potentiates proangiogenic activity of hepatocellular carcinoma cells
Journal
Oncotarget
Journal Volume
8
Journal Issue
49
Date Issued
2017-10-17
Author(s)
Wang, Han Yu
Li, Yong Shi
Lin, Hang
Hsu, Hung Wei
Huang, Chung Yi
Abstract
© Shao et al. Increased angiogenic activity has been demonstrated in hepatitis C virus (HCV)- related hepatocellular carcinoma (HCC), but the mechanism was unclear. To study the role of HCV core protein, we used tube formation and Matrigel plug assays to assess the proangiogenic activity of an HCC cell line, HuH7, and 2 of its stable clones-HuH7-corehigh and HuH7-core-low, with high and low HCV core protein expression, respectively. In both assays, HuH7-core-high and HuH7-core-low cells dose-dependently induced stronger angiogenesis than control cells. HuH7 cells with HCV core protein expression showed increased mRNA and protein expression of vascular endothelial growth factor (VEGF). VEGF inhibition by bevacizumab reduced the proangiogenic activity of HuH7- core-high cells. The promotor region of VEGF contains the binding site of activator protein-1 (AP-1). Compared with controls, HuH7-core-high cells had an increased AP-1 activity and nuclear localization of phospho-c-jun. AP-1 inhibition using either RNA knockdown or AP-1 inhibitors reduced the VEGF mRNA expression and the proangiogenic activity of HuH7-core-high cells. Among 131 tissue samples from HCC patients, HCV-related HCC revealed stronger VEGF expression than did hepatitis B virus-related HCC. In conclusion, increased VEGF expression through AP-1 activation is a crucial mechanism underlying the proangiogenic activity of the HCV core protein in HCC cells.
Subjects
Angiogenesis | Core protein | Hepatitis C virus | Hepatocellular carcinoma
Angiogenesis; Core protein; Hepatitis C virus; Hepatocellular carcinoma
SDGs
Other Subjects
bevacizumab; core protein; messenger RNA; RNA; transcription factor AP 1; vasculotropin; angiogenesis; Article; binding site; cancer tissue; cell clone; controlled study; Hepatitis C virus; Huh-7 cell line; human; human cell; liver carcinogenesis; liver cell carcinoma; promoter region; protein expression; protein function; protein localization; tumor vascularization
Type
journal article