Mechanisms of severe induction of aberrant DNA methylation by the shift from innate to acquired immunity

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07928
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hoshi University (2022-2023); National Cancer Center Japan (2021)
• Principal Investigator: Takeshima Hideyuki 星薬科大学, 先端生命科学研究所, 特任准教授 (40432497)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: エピジェネティクス / DNAメチル化 / 慢性炎症

Outline of Final Research Achievements

DNA methylation in 10 gastric mucosa samples with nodular gastritis and 13 gastric mucosa samples with atrophic gastritis was analyzed in genome-wide manner, and the cluster analysis was conducted. Six of the 10 samples with nodular gastritis formed a cluster with strong methylation, and 66 genes showed higher methylation levels in samples with nodular gastritis (increased methylation level: 10% or more). Tumor-suppressor genes, such as CDH1 and DAPK1, were more highly methylated in samples with nodular gastritis. In addition, TET2 and IDH1, which are involved in DNA demethylation, had only half the expression in samples with nodular gastritis.

Free Research Field

がんエピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

本研究により鳥肌胃炎に曝露することでエピゲノム異常誘発が加速すること、その標的遺伝子にはCDH1など未分化がんの発生に重要ながん抑制遺伝子が含まれていることが明らかになった。以上の成果は、未分化がんの発生メカニズムを解明するための基盤情報として極めて有用である。