Investigation of the molecular network regulated by novel tumor suppressive microRNAs in bladder cancer

• Project/Area Number: 16K20145
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Kagoshima University
• Principal Investigator: MATSUSHITA Ryosuke 鹿児島大学, 医歯学総合研究科, 客員研究員 (80735366)
• Research Collaborator: ENOKIDA Hideki 鹿児島大学, 医歯学域医学系, 准教授 (80347103) ; YOSHINO Hirofumi 鹿児島大学, 医歯学総合研究科, 客員研究員 (90642611) ; YONEMORI Masaya 鹿児島大学, 附属病院, 医員 (00758013) ; MIYAMOTO Kazutaka 鹿児島大学, 医歯学総合研究科, 大学院生
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: マイクロRNA / 膀胱癌 / 進行性膀胱癌 / microRNA / ゲノム

Outline of Final Research Achievements

Based on the microRNAs expression profile by next generation sequencing in bladder cancer (BC), we identified several downregulated microRNAs including miR-223, miR-199 family, miR-145-5p/3p, miR-139-5p/3p, miR-26a/b-5 and found their target tumor-associated genes in BC. Finally, we found that these microRNAs may have tumor-suppressive function via direct targeting of oncogenic genes including WDR62, CCNE1/2, UHRF1, PLOD2, and ITGA3. Thus, it was revealed that several important cancer signaling pathways like cell cycle, gene’s methylation, remodeling collagens in tumor matrix, and integrin signal might be regulated by microRNA network. According to these microRNA-axis study, we obtained basic data for new therapeutic strategy by using drugs that inhibit these signaling pathways.

Research Products

• [Journal Article] Regulation of ITGA3 by the dual-stranded microRNA-199 family as a potential prognostic marker in bladder cancer. (2017)
  • Author(s): Sakaguchi T, Yoshino H, Yonemori M, Miyamoto K, Sugita S, Matsushita R, Itesako T, Tatarano S, Nakagawa M, Enokida H.
  • Journal Title: British Journal of Cancer Volume: 116 Issue: 8 Pages: 1077-1087
  • DOI: 10.1038/bjc.2017.43
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dual tumor-suppressors miR-139-5p and miR-139-3p targeting matrix metalloprotease 11 in bladder cancer. (2016)
  • Author(s): Yonemori M, Seki N, Yoshino H, Matsushita R, Miyamoto K, Nakagawa M, Enokida H.
  • Journal Title: Cancer Science Volume: 107 Issue: 9 Pages: 1233-1242
  • DOI: 10.1111/cas.13002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tumour-suppressive miRNA-26a-5p and miR-26b-5p inhibit cell aggressiveness by regulating PLOD2 in bladder cancer (2016)
  • Author(s): Miyamoto K, Seki N, Matsushita R, Yonemori M, Yoshino H, Nakagawa M, Enokida H.
  • Journal Title: British Journal of Cancer Volume: 115 Issue: 3 Pages: 354-363
  • DOI: 10.1038/bjc.2016.179
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Regulation of UHRF1 by dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR 145-3p): class FormattedString { value: Inhibition of bladder cancer cell aggressiveness } (2016)
  • Author(s): Matsushita R, Yoshino H, Enokida H, Goto Y, Miyamoto K, Yonemori M, Inoguchi S, Nakagawa M, Seki N.
  • Journal Title: Oncotarget Volume: 7 Issue: 19 Pages: 28460
  • DOI: 10.18632/oncotarget.8668
  • URL: https://localhost/en/publications/c60002b3-2a7f-4967-bd88-b12428c875d1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Tumor-suppressive microRNA-26a-5p/-26b-5p inhibit cancer cell migration and invasion through targeting PLOD2 that is a potential prognostic marker in bladder cancer (2017)
  • Author(s): Kazutaka Miyamoto, Kagoshima, Japan, Naohiko Seki, Ryosuke Matsushita, Masaya Yonemori, Hirofumi Yoshino, Takashi Sakaguchi, Satoshi Sugita, Hideki Enokida, Masayuki Nakagawa
  • Organizer: 米国泌尿器科学会
  • Int'l Joint Research
• [Presentation] Tumor-suppressive microRNA-26a-5p/-26b-5p inhibit cancer cell migration and invasion through targeting PLOD2 that is a potential prognostic marker in bladder cancer. (2017)
  • Author(s): Miyamoto K, Seki N, Matsushita R, Yonemori M, Yoshino H, Sakaguchi T, Sugita S, Enokida H, Nakagawa M.
  • Organizer: American Urological Association (AUA) annual meeting
  • Place of Presentation: Boston (USA)
  • Int'l Joint Research
• [Presentation] Dual tumor-suppressors (miR-145-5p/miR-145-3p) inducing cancer cell apoptosis via direct targeting UHRF1 in bladder cancer (2016)
  • Author(s): Matsushita R, Seki N, Yoshino H, Miyamoto K, Yonemori M, Kurozumi A, Goto Y, Enokida H, Nakagawa M.
  • Organizer: American Urological Association (AUA) annual meeting
  • Place of Presentation: San Diego (USA)
  • Int'l Joint Research
• [Presentation] Dual tumor-suppressors miR-139-5p/-3p derived from pre-miR-139 via targeting matrix metalloprotease 11 (MMP11) in bladder cancer (2016)
  • Author(s): Yonemori M, Seki N, Matsushita R, Miyamoto K, Yoshino H, Goto Y, Kato M, Kurozumi A, Nakagawa M, Enokida H
  • Organizer: American Urological Association (AUA) annual meeting
  • Place of Presentation: San Diego (USA)
  • Int'l Joint Research