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

Research Project

Project/Area Number 17H04332
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKagoshima 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
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
KeywordsマイクロRNA / 膀胱癌 / 癌遺伝子 / miRNA 223 / WDR62 / 膀胱がん / ゲノム編集 / ゲノム編集技術
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.

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。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (6 results)

All 2019 2018 2017 Other

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] Tumor suppressive microRNA223 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: 54 Pages: 2222-2236

    • DOI

      10.3892/ijo.2019.4762

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HRAS as a potential therapeutic target of salirasib RAS inhibitor in bladder cancer.2019

    • 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

    • DOI

      10.3892/ijo.2018.4435

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [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
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 膀胱癌におけるRAS阻害剤Salirasibを介した治療標的としてのHRAS2018

    • Author(s)
      杉田 智,吉野裕史,宮元一隆,大迫洋一,坂口 大,米森雅也,榎田英樹,中川昌之.
    • Organizer
      第106回日本泌尿器科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Regulation of ITGA3 by the dual-stranded microRNA-199 family as a potential prognostic marker in bladder cancer.2018

    • Author(s)
      Sakaguchi T
    • Organizer
      2018 AUA annual meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 鹿児島大学大学院医歯学総合研究科 腫瘍学講座泌尿器科学分野

    • URL

      http://www.kufm.kagoshima-u.ac.jp/~urology/

    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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