Analysis of novel miR-143/p38 signaling in mice and human breast cancer cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07431
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Chubu University
• Principal Investigator: Iwamoto Takashi 中部大学, 生命健康科学部, 教授 (60223426)
• Co-Investigator(Kenkyū-buntansha): 喬 善楼 中部大学, 生命健康科学部, 教授 (00343658) ; 岩田 悟 中部大学, 実験動物教育研究センター, 助教 (70722891)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: マイクロRNA / 心筋症 / p38

Outline of Final Research Achievements

We found that the expression of p38 was downregulated in the hearts of the transgenic mice expressing miR-143 (alpha MHC/143/145TG) at a high level. We made a series of mice which had various deletion in the 3’UTR of p38 and crossed them with alpha MHC/143/145TG mice. We found that the deletion of about 200 base pairs containing one possible target site for miR-143 restored about half of p38 expression suppression in alpha MHC/143/145TG mice hearts, suggesting that overexpression of miR-143 actually suppressed p38 expression in the mouse hearts. When about 3200 base pairs of p38 3’UTR was deleted, the deletion of miR-143 significantly increased p38 expression　in the bladders and small intestines. These data suggest that the targets of miRNA that are not conserved among mammals may function in living animals in certain situation.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

マイクロRNAは20塩基程度の小さなRNAでヒトでは2000種類以上あり、mRNAの発現を調節しており、多くの生物種での発達や生理機能に重要なだけではなく、癌や多くの疾患に関与している。その標的配列の探索において多くの生物種で保存されている事が大きな基準になっている。今回の研究で、哺乳類間で保存されていないマイクロRNAでも、ある条件下では生体で機能する事が示唆された。