Development of a novel method for diagnosis and therapy of bladder cancer using miRNA-146a-5p and its functional analysis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16759
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Usuba Wataru 聖マリアンナ医科大学, 医学部, 助教 (90867649)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: miR-146a-5p / 膀胱癌 / エクソソーム / TET2 / 膀胱腔内注入療法 / 血管新生

Outline of Final Research Achievements

Focusing on miR-146a-5p, which is upregulated in the urine of bladder cancer patients, we conducted research to elucidate the mechanism of action of miR-146a-5p on bladder cancer and to apply it to novel therapeutic methods.
As a target gene of miR-146a-5p, TET2 was identified by microarray gene expression analysis. In vitro experiments using bladder cancer cells and vascular endothelial cells showed that TET2 promotes angiogenesis of bladder cancer via c-Myc. Suppression of TET2 by miR-146a-5p in a mouse model promotes tumor growth and angiogenic potential of bladder cancer. Kaplan-Meier survival analysis of bladder cancer patients showed that low TET2 expression and/or high c-Myc expression were poor prognostic factors.
These results suggest that miR-146a-5 may be useful as a therapeutic target for bladder cancer.

Free Research Field

泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

miRNAは1種類で同じパスウェイに存在する複数の遺伝子を標的とすることができる。よって強固な機能抑制が期待できるため、miRNAはsiRNAと比べ新規治療標的として効果的である。今回の研究ではmiR-146a-5pが膀胱癌の成長を促進することが示された。この結果を用いてmiR-146a-5pの膀胱内注入療法を確立し発現制御が可能となれば、これまでにない新規・再発治療法の早期実現に繋がり、さらにmiR-146a-5pにより制御を受ける他癌腫に対しての効果も期待できる。