Functional analysis of the oncogenic microRNA by the genome editing aiming at the development of the innovative renal cancer treatment

• Project/Area Number: 17K11148
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Kagoshima University
• Principal Investigator: ITESAKO Toshihiko 鹿児島大学, 医歯学総合研究科, 客員研究員 (10642613)
• Co-Investigator(Kenkyū-buntansha): 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: マイクロRNA / 腎癌 / CRISPR/Cas9 / microRNA / 膀胱癌 / ゲノム編集

Outline of Final Research Achievements

As results of research, we found that microRNA-210 (miR-210) was highly expressed in renal cancers compared to normal kidneys by the array analysis using normal kidneys and kidney cancer clinical specimens. miR-210 expression was almost depleted by using CRISPR/Cas9. It was revealed that miR-210 regulated TWIST1 directly by the target gene search. In addition, we confirmed that miR-1274 was highly expressed in kidney cancers compared to normal kidneys, and identified BMPR1B which was an osteoplasty protein receptor as the target gene. In summary, we showed a functional analysis and a target gene of highly expressed micro RNA in renal cancer.

Academic Significance and Societal Importance of the Research Achievements

進行性腎癌の多くは分子標的治療薬に治療抵抗性を獲得し、再発・転移に至る。マイクロRNAは遺伝子の発現調節に寄与することが知られており、今まで癌に関与するマイクロRNAに関して多くの報告がなされてきた。しかし、癌部で発現が亢進しているマイクロRNAに関しての報告は限定的であった。本研究により、癌促進型マイクロRNAの機能解析と標的遺伝子を示すことができ、進行性腎癌に対する新たな理解と治療戦略の可能性が提案された。

Research Products

• [Journal Article] Potential tumor-suppressive role of microRNA-99-3p in sunitinib-resistant renal cell carcinoma cells through the regulation of RRM2 (2019)
  • Author(s): Osako Y, Yoshino H, Sakaguchi T, Sugita S, Yonemori M, Nakagawa M, Enokida H.
  • Journal Title: International Journal of Oncology Volume: 54 Pages: 1759-1770
  • DOI: 10.3892/ijo.2019.4736
  • Peer Reviewed / Open Access
• [Journal Article] Tumor-suppressive microRNA-223 targets WDR62 directly in bladder cancer. (2019)
  • Author(s): Sugita S, Yoshino H, Yonemori M, Miyamoto K, Matsushita R, Sakaguchi T, Itesako T, Tatarano S, Nakagawa M, Enokida H.
  • Journal Title: Int J Oncol. Volume: -
  • Peer Reviewed
• [Journal Article] Regulation of ITGA3 by the dual-stranded microRNA-199 family as a potential prognostic marker in bladder cancer. (2018)
  • Author(s): Sakaguchi T, Yoshino H, Yonemori M, Miyamoto K, Sugita S, Matsushita R, Itesako T, Tatarano S, Nakagawa M, Enokida H.
  • Journal Title: Br J Cancer Volume: 118
  • Peer Reviewed
• [Journal Article] PHGDH as a Key Enzyme for Serine Biosynthesis in HIF2α-Targeting Therapy for Renal Cell Carcinoma. (2017)
  • Author(s): Yoshino H, Nohata N, Miyamoto K, Yonemori M, Sakaguchi T, Sugita S, Itesako T, Kofuji S, Nakagawa M, Dahiya R, Enokida H.
  • Journal Title: Cancer Res Volume: 77 Pages: 6321-6329
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Targeting PHGDH exerts anti-omcogenic effects in bladder cncer. (2019)
  • Author(s): Yoshino H
  • Organizer: 第34回欧州泌尿器学会議（EAU19）
  • Int'l Joint Research