2023 Fiscal Year Final Research Report

Roles of p53-dependent long non-coding RNAs in adipose tissues and blood vessels

Research Project

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Project/Area Number	21H02974
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 54040:Metabolism and endocrinology-related
Research Institution	Chiba University
Principal Investigator	Hashimoto Naoko 千葉大学, 大学院医学研究院, 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) OSHIMA JUNKO 千葉大学, 大学院医学研究院, 特任教授 (80792275)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	細胞老化IncRNA / 転写因子p53 / 脂肪細胞 / 加齢性疾患
Outline of Final Research Achievements	We aimed to identify p53-dependent long non-coding RNAs (lncRNAs) in adipose tissue and vascular endothelial cells that are link to senescence. In addition, we aimed to elucidate the role of p53-lncRNAs and their epigenomic regulation in endocrine and metabolic diseases. Since p53 is also important in stemness, we identified p53-dependent lncRNAs and investigated their role in the survival and stemness maintenance of human ES cells. We found that one of the p53-lncRNAs suppresses key stemness genes, increases the TGF-β signaling pathway, and induces the differentiation of stem cells into fibroblast-like cells. As lncRNAs can act as miRNA sponges, we also focused on miRNAs that link aging and cancer. We investigated the mechanism of miR-874-mediated tumor suppression in breast cancer cells. miR-874 overexpression activates p53/Myc pathway and suppresses the mevalonate pathway, suggesting that these non-coding RNAs may have a role in the pathological regulation of cancer and aging.
Free Research Field	内分泌代謝学
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、細胞老化や幹細胞において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発見し、これらががんや老化の病態制御に影響する可能性が示唆された。今後、これらのlncRNAが健康長寿へ向けたバイオマーカーや、核酸医薬品などのがん治療に関する創薬の開発に発展することが期待される。