Exploring novel therapeutic strategies for treatment-resistant bladder cancer using miRNAs in exosomes as a starting point

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09430
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Kagoshima University
• Principal Investigator: YAMADA Yasutoshi 鹿児島大学, 医歯学域鹿児島大学病院, 准教授 (40437968)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 膀胱癌 / 治療抵抗 / エクソソーム

Outline of Final Research Achievements

As a result of this study, we performed RNA sequencing analysis using patient-derived bladder urothelial carcinoma (n=3), bladder cancer CIS (n=3), and renal pelvis ureteral urothelial carcinoma (n=3) serum exosomal RNAs and confirmed that the aspect of exosome-containing nucleic acids was completely different in urothelial carcinoma compared with normal samples. Next, we focused on BYCRN1, one of the LncRNAs among the candidate nucleic acids, and investigated its expression in serum exosomal RNA, and found that its expression was significantly increased in patients with urothelial carcinoma compared to healthy controls. Furthermore, knockdown of BYCRN1 showed an antitumor effect, and when expression was examined in pre- and postoperative samples, expression decreased after surgery. These results are summarized in the paper.

Free Research Field

泌尿器癌

Academic Significance and Societal Importance of the Research Achievements

現在、臨床的に感度・特異度ともに有用な尿路上皮癌（腎盂尿管癌および膀胱癌）の腫瘍マーカーは無く、患者は放射線被曝を伴うCT検査や侵襲の大きな尿管鏡検査や膀胱鏡検査が一般的に行われている。そこで、エクソソーム含有核酸を用いて尿路上皮癌に対する腫瘍マーカーとなる核酸を検出することを本研究の目的としたが、我々の研究成果は血清エクソソーム中のBCYRN1が尿路上皮癌患者で有意に高く、また術後に発現が低下した。更にBCYRN1をノックダウンすることで抗腫瘍効果が得られることを確認し、エクソソーム中RNAを起点とした治療抵抗性膀胱癌に対する新規治療戦略の一歩を踏み出したと考える。