The role of protein kinase R (PKR) for hepatocarcinogenesis and progression of hepatocellular carcinoma during inflammation due to hepatitis C virus infection.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09006
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Ehime University
• Principal Investigator: Hiasa Yoichi 愛媛大学, 医学系研究科, 教授 (70314961)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: Protein kinase R / Hepatocellular carcinoma / C型肝炎ウイルス / eIF2-alpha / PERK / ERストレス / DNMT / MAPK

Outline of Final Research Achievements

Protein kinase R (PKR) is recognized as a key executor of anti-hepatitis C virus (HCV). Moreover, over-expressed PKR up-regulates the mitogen-activated protein kinase (MAPK) signaling pathway, and it promotes hepatocarcinogenesis and progression of hepatocellular carcinoma (HCC) in vitro models. In this study, we investigate the total potential of PKR against the role for HCC by using in vivo models, including human specimens after HCC resection and HCC transplanted nude mice model. In also human specimens, over-expressed PKR enhanced MAPK signaling, and in mice model, PKR inhibitor inhibited progression of HCC. Additionally, PKR has epigenetic roles to regulate DNMTs in HCV infected cells. Moreover, there is not obvious interaction between PKR and PERK, and PKR would regulate the activity of eIF2-alpha cooperated with PERK, which is a key molecule for ER stress and cell inflammation. From those data, PKR could be one of the therapeutic targets to regulate HCC in patients with HCV.

Free Research Field

医歯薬学