Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 6135715794, Iran.
The Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran.
World J Gastroenterol. 2019 Jan 7;25(1):42-58. doi: 10.3748/wjg.v25.i1.42.
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.
肝细胞癌（HCC）是第五种最常见的癌症，丙型肝炎病毒（HCV）感染在 HCC 的发展中起着主要作用。HCV 感染导致 HCC 的分子机制多种多样。HCV 核心蛋白是 HCV 相关肝脏发病机制中的一个重要危险因素，可调节细胞周期调控、细胞生长促进、细胞增殖、凋亡、氧化应激和脂质代谢等多个信号通路。HCV 核心蛋白对转化生长因子β（TGF-β）、血管内皮生长因子（VEGF）、Wnt/β-连环蛋白（WNT）、环氧化酶-2（COX-2）和过氧化物酶体增殖物激活受体α（PPARα）等信号通路的失调与 HCC 的发生有关。因此，有人认为该蛋白可被视为进一步研究 HCC 发病机制的一个有利靶点。此外，鉴于这些信号通路在 HCC 中的轴作用，它们被认为是癌症治疗的可用药靶。因此，使用策略来限制核心蛋白对这些信号通路的失调作用似乎对于预防 HCV 相关 HCC 是必要的。
