Functional analyses of oncogenic microRNA by genome editing and development of innovative genome-based drug discovery for bladder cancer.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04332
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Kagoshima University
• Principal Investigator: ENOKIDA Hideki 鹿児島大学, 医歯学域医学系, 准教授 (80347103)
• Co-Investigator(Kenkyū-buntansha): 中川 昌之 鹿児島大学, 医歯学域医学系, 教授 (90164144) ; 吉野 裕史 鹿児島大学, 医歯学域鹿児島大学病院, 助教 (90642611)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: マイクロRNA / 膀胱癌 / 癌遺伝子

Outline of Final Research Achievements

Based on the microRNA expression analyses by next generation sequencing, Patients with high expression of miR-199 family showed poorer prognosis compared to the counter pert. The mirs function as tumor suppressive miRNA via suppressing Integrin signals. On the other hand, miR-223 transfection to bladder cancer cell lines showed inhibitions of cell proliferation, migration, and invasion as well as inducing cell apoptosis. Furthermore, Sarilasib, an antagonist to HRAS showed inhibitions of cell proliferation, migration, and invasion with or without HRAS mutations. We also found that the patients with high expression of PHGDH gene involved in Serine synthesis pathway had poorer prognosis, and it was associated with Gemcitabine and cisplatin chemo-resistance in patients with bladder cancer.

Free Research Field

泌尿器癌

Academic Significance and Societal Importance of the Research Achievements

今回の成果でマイクロRNAを基点とした膀胱癌の増殖/転移に関わるいくつかの重要な分子経路が明らかになった。その経路を遮断する治療薬候補も同定出来て画期的であった。さらに他の治療薬の開発に繋がるため、次の段階への大きな礎となりうる。本研究の成功は、現在、有効な治療法の少ない進行性膀胱癌患者に対して大きな福音をもたらすと思われる。