Development of novel nucleic acid treatment through nano-micelles delivering tumor suppressive microRNA in bladder cancer

• Project/Area Number: 26293354
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• 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): 関 直彦 千葉大学, 大学院医学研究院, 准教授 (50345013) ; 中川 昌之 鹿児島大学, 医歯学域医学系, 教授 (90164144) ; 千代丸 剛 鹿児島大学, 医学部・歯学部附属病院, 助教 (60593796)
• Co-Investigator(Renkei-kenkyūsha): KATAOKA Kazunori 東京大学, 疾患生命工学センター, 教授 (00130245) ; MIYATA Kanjiro 東京大学, 疾患生命工学センター, 准教授 (50436523)
• Research Collaborator: INOGUCHI Satoru 鹿児島大学, 医歯学総合研究科, 大学院生 ; ISHIHARA Tomoaki 鹿児島大学, 医歯学総合研究科, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: マイクロRNA / 膀胱癌 / ナノミセル / 癌抑制型マイクロRNA

Outline of Final Research Achievements

Based on the microRNAs expression profile by next generation sequencing in bladder cancer, we identified several tumor suppressive microRNAs including miR-23b/24/27b, miR-144-5p/3p, miR-26a/b-5, and miR-199 family and found their target tumor-associated genes. Next, we established nano-micelles carrier containing tumor suppressive miR-218 and administrated it intravenously to xenograft model mice. Finally, we confirmed that the red-pigmented carrier was successfully delivered to cancer tissues.

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: Br J Cancer Volume: 116 Pages: 1077-1087
  • DOI: 10.1038/bjc.2017.43
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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 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 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): 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 Pages: 28460-28487
  • DOI: 10.18632/oncotarget.8668
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tumour-suppressive microRNA-144-5p directly targets CCNE1/2 as potential prognostic markers in bladder cancer. (2015)
  • Author(s): Ryosuke Matsushita
  • Journal Title: British Journal of Cancer Volume: 113 Pages: 282-289
  • DOI: 10.1038/bjc.2015.195
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Dual regulation of receptor tyrosine kinase genes EGFR and c-Met by the tumor-suppressive microRNA-23b/27b cluster in bladder cancer. (2015)
  • Author(s): Chiyomaru T, Seki N, Inoguchi S, Ishihara T, Mataki H, Matsushita R, Goto Y, Nishikawa R, Tatarano S, Itesako T, Nakagawa M, Enokida H.
  • Journal Title: International Journal of Oncology Volume: 46 Pages: 487-496
  • DOI: 10.3892/ijo.2014.2752
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tumour-suppressive microRNA-24-1 inhibits cancer cell proliferation through targeting FOXM1 in bladder cancer. (2014)
  • Author(s): Inoguchi S, Seki N, Chiyomaru T, Ishihara T, Matsushita R, Mataki H, Itesako T, Tatarano S, Yoshino H, Goto Y, Nishikawa R, Nakagawa M, Enokida H.
  • Journal Title: FEBS letter Volume: 588 Pages: 3170-3179
  • DOI: 10.1016/j.febslet.2014.06.058
  • 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 maker 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): Ryosuke Matsushita
  • Organizer: American Urological Association Annual Meeting
  • Place of Presentation: San Diego ( USA )
  • Year and Date: 2016-05-06
  • 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
• [Presentation] Pre-microRNA-145 (miR-145-5p/miR-145-3p) function (2015)
  • Author(s): 松下 良介
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] MicroRNA-144-5p functions as tumor suppressor through targeting cyclin E1/E2 that are potential prognostic markers in bladder cancer (2015)
  • Author(s): Ryosuke Matsushita
  • Organizer: American Urological Association Annual Meeting
  • Place of Presentation: New Orleans ( USA )
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] Tumor suppressive microRNA-24 inhibits bladder cancer through regulation of FOXM1 (2014)
  • Author(s): 井口 智生
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜市・パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Tumor suppressive microRNA-24 inhibits bladder cancer via targeting transcription factor FOXM1 (2014)
  • Author(s): Satoru Inoguchi
  • Organizer: 2014 AUA annual meeting
  • Place of Presentation: Orland, USA
  • Year and Date: 2014-05-16 – 2014-05-21
• [Remarks] 千葉大学大学院医学研究院 先端医学応用講座 機能ゲノム学
  • URL: http://genomejet.jp/research/