Analysis of epigenetic changes via histone modification in liver cancer and development of new therapeutic strategy

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09021
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: SAITO Hidetsugu 慶應義塾大学, 薬学部(芝共立), 教授 (80186949)
• Research Collaborator: KAMADA Nobuhiko University of Michigan, Center for Microbial Systems ; SAITO Yoshimasa ; MASHINO Tadahiko ; KIMURA Masaki ; YAMADA Shoji ; NAKAOKA Toshiaki
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 脂肪性肝炎 / 肝発癌 / エピジェネティック変化 / mTOR / Nrf-2 / EZH2 / microRNA-122 / 高脂肪食摂餌

Outline of Final Research Achievements

The main cause of hepatocarcinogenesis in Japan has been changing from viral infection to fatty liver diseases. The hepatic pathogenesis in fatty liver diseases is considered to be induced by dietary environmental change and this fact indicated that epigenetic change is an important factor in this disease entity. We refined Nrf-2, EZH2 and microRNA-122 as pathogenetic factors from the analyses of HCV particle producing cell line HPI and a murine model STAM. Moreover, we focused on a C57BL/6 model which develops hepatoma with only a high fat diet without giving any chemical carcinogens, and obtained an important result from this murine model that a component change of bile acids metabolized by intestinal microbiota and a consequent activation of mTOR pathway were most notable pathogenetic factors. Nrf-2, EZH2 and microRNA were also changed in this model, and these results reflected in vitro aspects.

Free Research Field

消化器内科