Elucidation of the expression mechanism of microRNAs and related molecules useful for differentiating flat type urothelial tumors

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16590
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Nara Medical University
• Principal Investigator: Morita Kohei 奈良県立医科大学, 医学部, 助教 (60533718)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 尿路上皮癌 / microRNA

Outline of Final Research Achievements

Urothelial carcinoma (UC) typically occurs in the urinary system and is the most common type of bladder cancer. The nucleus accumbens-associated protein 1 (NACC1) is a transcription factor constitutively expressed in the urothelium, where it regulates cell growth, senescence, autophagy, and epithelial-mesenchymal transition.
Immunohistochemical analysis of TUR-BT specimens revealed that over 70% of UC cells presented strongly positive results for NACC1. Functional experiments involving miR-331-3p and its target molecule NACC1 were conducted using the UC cell lines, T24, UMUC6, and KU7. Overexpression of miR-331-3p resulted in significantly suppressed NACC1 mRNA and cell proliferation in these cell lines, and reduce cell proliferation, migration. Cell senescence via cell cycle arrest at the G1 phase was induced by NACC1 inhibition. These findings suggest that NACC1 regulated bymiR-331-3p, plays a key role in UC cell proliferation and invasion.

Free Research Field

病理診断学

Academic Significance and Societal Importance of the Research Achievements

尿路上皮癌は再発を繰り返す腫瘍である。膀胱鏡による低侵襲治療も行われているが、筋層浸潤を認める場合は原則的に膀胱摘出となる。筋層浸潤の有無が生命予後及びQOLに大きな影響を及ぼすため、それらの防止、及び早期発見が重要である。
申請者は尿路上皮癌切除検体、及び細胞株において、NACC1及びmicroRNA-331-3Pと腫瘍の浸潤・進展能との関連性を見出すことができた。NACC1をターゲットとした治療介入により、これらの浸潤能を制御できる可能性があり、尿路上皮癌の予後改善に寄与できる可能性がある。