Elucidation of the mechanism of cellular senescence via senescence-associated lncRNA and p53 transcription complex

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07439
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Chiba University
• Principal Investigator: Hashimoto Naoko 千葉大学, 大学院医学研究院, 特任助教 (10724875)
• Co-Investigator(Kenkyū-buntansha): 田中 知明 千葉大学, 大学院医学研究院, 教授 (50447299) ; 高野 博之 千葉大学, 大学院薬学研究院, 教授 (60334190)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 細胞老化 / ncRNA / エピゲノム / 動脈硬化

Outline of Final Research Achievements

As the population ages, the prevalence of age-related diseases such as cancer, diabetes and atherosclerosis has increased over years. The contribution of epigenetic regulation to the age-associated pathophysiology has been gradually unraveled. In the present study, using next generation sequencing (NGS)-based RNA-seq and ChIP-seq, we identified several candidate sequences of long non-coding RNAs (lncRNAs) upregulated specifically in senescent cells and performed functional analysis. As tumor suppressor p53 also plays a key role in maintaining pluripotency, we focused on the tumor suppressor p53 and p53-responsive lncRNAs upregulated specifically in human embryonic stem (ES) cells. We found that one of the p53-responsive lncRNAs contributes to the maintenance of pluripotency in ES cells. These results indicate the multifaceted functions of p53 and lncRNAs.

Free Research Field

代謝内科学

Academic Significance and Societal Importance of the Research Achievements

高齢化に伴い、がん、糖尿病や高血圧、動脈硬化症などの加齢疾患の発症が増加している。長鎖非コードRNA（lncRNA）は、エピゲノム制御を介して発生やがんなど様々な生命現象に重要であることがわかってきた。本研究によって、細胞老化に伴い複数の長鎖非コードRNAがp53依存的に発現誘導されることを解明し、老化の病態制御に影響する可能性が示唆された。今後、加齢疾患の予防や治療、健康長寿へ向けたバイオマーカーや創薬の開発に発展することが期待される。