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Development of the innovative treatment based on the search of microRNA blocking growth signals in urothelial carcinoma

Research Project

Project/Area Number 16K11015
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionKagoshima University

Principal Investigator

YOSHINO Hirofumi  鹿児島大学, 医歯学域附属病院, 助教 (90642611)

Co-Investigator(Kenkyū-buntansha) 関 直彦  千葉大学, 大学院医学研究院, 准教授 (50345013)
Research Collaborator Matsushita Ryousuke  
Miyamoto Kazutaka  
Yonemori Masaya  
Enokida Hideki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsマイクロRNA / 尿路上皮癌 / miRNA-199 / miRNA-223 / 治療標的型マイクロRNA / 癌 / 核酸 / シグナル伝達
Outline of Final Research Achievements

We elucidated that expression levels of miRNA-199a-3p/-5p, miRNA-199b-3p/-5p, and miRNA-223 were significantly down regulated in bladder cancer tissues, and that transduction of these miRNA suppressed cell proliferation, migration, and invasion. We also elucidated that miRNA-199 and miRNA-223 individually controlled ITGA3 and WDR62 directly. We finally succeeded to publish these data in journals.
In addition, we succeeded in the establishment of cancer cells which resistant to gemcitabine or cisplatin, and made profiles of miRNA with performed next-generation sequencing analyses. We found that miRNA-486-5p was down regulated in cisplatin-resistant cancer cells according to the profiles, and that miRNA-486-5p transduction suppressed cell proliferation in these cells.

Academic Significance and Societal Importance of the Research Achievements

1「治療標的探索型miRNA」を起点として、尿路上皮癌の再発や治療抵抗性に関わる機能性RNA分子ネットワークの探索を行い、いくつかの治療標的型miRNAを同定し論文化することができた。これらの成果により、miRNAを用いた尿路上皮癌の治療の可能性が示唆された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (18 results)

All 2019 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (8 results) (of which Int'l Joint Research: 4 results)

  • [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: -

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potential tumor-suppressive role of microRNA-99a-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

      Int J Oncol.

      Volume: -

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HRAS as a potential therapeutic target of salirasib RAS inhibitor in bladder cancer.2018

    • Author(s)
      Sugita S, Enokida H, Yoshino H, Miyamoto K, Yonemori M, Sakaguchi T, Osako Y, Nakagawa M.
    • Journal Title

      Int J Oncol.

      Volume: 53 Pages: 725-736

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bromodomain protein BRD4 inhibitor JQ1 regulates potential prognostic molecules in advanced renal cell carcinoma.2018

    • Author(s)
      Sakaguchi T, Yoshino H, Sugita S, Miyamoto K, Yonemori M, Osako Y, Meguro-Horike M, Horike SI, Nakagawa M, Enokida H.
    • Journal Title

      Oncotarget

      Volume: 9 Pages: 23003-23017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Downregulation of microRNA-1274a induces cell apoptosis through regulation of2018

    • Author(s)
      Yoshino H, Yonezawa T, Yonemori M, Miyamoto K, Sakaguchi T, Sugita S, Osako Y, Tatarano S, Nakagawa M, Enokida H.
    • Journal Title

      Oncol Rep

      Volume: 39 Pages: 173-181

    • DOI

      10.3892/or.2017.6098

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] microRNA-210-3p depletion by CRISPR/Cas9 promoted tumorigenesis through revival of TWIST1 in renal cell carcinoma.2017

    • Author(s)
      Yoshino H, Yonemori M, Miyamoto K, Tatarano S, Kofuji S, Nohata N, Nakagawa M, Enokida H.
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 13 Pages: 20881-20894

    • DOI

      10.18632/oncotarget.14930

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] PHGDH as a Key Enzyme for Serine Biosynthesis in HIF2α-Targeting Therapy for2017

    • 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

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [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

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tumour-suppressive miRNA-26a-5p and miR-26b-5p inhibit cell aggressiveness by regulating PLOD2 in bladder cancer2016

    • 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

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / 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 Issue: 9 Pages: 1233-1242

    • DOI

      10.1111/cas.13002

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Targeting PHGDH exerts anti-oncogenic effects in bladder cancer2019

    • Author(s)
      Hirofumi Yoshino
    • Organizer
      欧州泌尿器科学
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The tumor suppressor microRNA-223 targets WDR62 directly in bladder cancer2018

    • Author(s)
      Satoshi Sugita
    • Organizer
      米国泌尿器科学会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Targeting metabolism re-programming as a therapy for drug-resistant renal cell carcinoma2018

    • Author(s)
      Hirofumi Yoshino, Kazutaka Miyamoto, Masaya Yonemori, Satoru Sugita, Takashi Sakaguchi, Hideki Enokida, Masayuki Nakagawa
    • Organizer
      欧州泌尿器科学会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膀胱癌におけるIntegrin α3(ITGA3)制御を介したmicroRNA-199 familyの癌抑制的作用2017

    • Author(s)
      坂口 大、吉野裕史、米森雅也、宮元一隆、杉田 智、松下良介、榎田英樹、中川昌之
    • Organizer
      第105回日本泌尿器科学会総会
    • Place of Presentation
      かごしま県民交流センター(鹿児島県鹿児島市)
    • Year and Date
      2017-04-21
    • Related Report
      2016 Research-status Report
  • [Presentation] CRISPR/Cas9-mediated miR-20-3p depletion promoted tumorigenesis through revival of TWIST in renal cell carcinoma2017

    • Author(s)
      Hirofumi Yoshino, Masaya Yonemori, Kazutaka Miyamoto, Satoshi Kofuji, Nijiro Nohata, Hideki Enokida, Masayuki Nakagawa
    • Organizer
      米国泌尿器科学会
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] CRISPR/CAas9によるmicroRNA編集による腎癌の進展メカニズムの解明2017

    • Author(s)
      吉野裕史、米森雅也、宮元一隆、榎田英樹、中川昌之
    • Organizer
      日本泌尿器科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Tumor suppressive miRNA-26a/b inhibit cell migration and invasion through targeting a prognostic marker, Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in bladder cancer.2016

    • Author(s)
      Miyamoto K, Seki N, Matsushita R, Yonemori M, Yoshino H, Nakagawa M, Enokida H.
    • Organizer
      第68回西日本泌尿器科学会
    • Place of Presentation
      海峡メッセ下関(山口県下関市)
    • Year and Date
      2016-11-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Dual-strands of microRNA-139 (miR-139-5p and miR-139-3p) targeting matrix metalloprotease 11 (MMP11) in bladder cancer2016

    • Author(s)
      Yonemori M, Seki N, Yoshino H, Matsushita R, Miyamoto K, Nakagawa M, Enokida H.
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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