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Elucidation of molecular pathway of benign prostatic hyperplasia and prostate cancer based on microRNA.

Research Project

Project/Area Number 18K16685
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56030:Urology-related
Research InstitutionChiba University

Principal Investigator

YAMADA YASUTAKA  千葉大学, 医学部附属病院, 医員 (30814595)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords前立腺癌 / 前立腺肥大症 / マイクロRNA / 去勢抵抗性前立腺癌 / エクソソーム / 治療抵抗性 / microRNA
Outline of Final Research Achievements

miRNA expression signatures by RNA sequencing showed that the miR-455-duplex (miR-455-5p and miR-455-3p) acted as antitumor miRNAs in prostate cancer(PCa) cells. Based on a large patient cohort in The Cancer Genome Atlas, expression of eight miR-455-5p/-3p target genes (PIR: P = 0.0137, LRP8: P = 0.0495, IGFBP3: P = 0.0172, DMBX1: P = 0.0175, CCDC64: P = 0.0446, TUBB1: P = 0.0149, KIF21B: P = 0.0336, and NFAM1: P = 0.0013) was significantly associated with poor prognosis of PCa patients. Here, we focused on PIR (pirin), a highly conserved member of the cupin superfamily. PIR expression was directly regulated by miR-455-5p, and PIR overexpression was detected in hormone-sensitive prostate cancer (HSPC) surgical specimens and CRPC autopsy specimens. Loss-of-function assays using siRNA or an inhibitor (bisamide) showed that downregulation of PIR expression blocked cancer cell migration and invasion. PIR might be a promising diagnostic marker and therapeutic target for HSPC and CRPC.

Academic Significance and Societal Importance of the Research Achievements

本研究期間中に我々は、新規癌抑制型マイクロRNAを起点とした機能性RNA分子ネットワーク解析を行い、治療抵抗性前立腺癌における新規治療標的分子を探索した。これまでの治療抵抗性前立腺癌における治療の中心として、アンドロゲン受容体を標的としたより強力な抗アンドロゲン剤であったが、本研究結果から得られた候補分子は既存の治療とは異なる経路を標的とするものであり、新たな治療戦略としての可能性を示したといえる。ホルモン依存性の癌である前立腺癌において、アンドロゲン非依存性に増殖能を獲得した治療抵抗性前立腺癌に対する新規治療法の開発は、罹患数の増加が顕著な前立腺癌治療において非常に意義の大きいものである。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Replisome genes regulation by antitumor miR-101-5p in clear cell renal cell carcinoma2020

    • Author(s)
      Yamada Yasutaka、Nohata Nijiro、Uchida Akifumi、Kato Mayuko、Arai Takayuki、Moriya Shogo、Mizuno Keiko、Kojima Satoko、Yamazaki Kazuto、Naya Yukio、Ichikawa Tomohiko、Seki Naohiko
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 4 Pages: 1392

    • DOI

      10.1111/cas.14327

    • URL

      https://pure.teikyo.jp/en/publications/e92beaee-6a74-426b-810a-30b26ba11419

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aberrantly expressed PLOD 1 promotes cancer aggressiveness in bladder cancer: a potential prognostic marker and therapeutic target2019

    • Author(s)
      Yamada Yasutaka、Kato Mayuko、Arai Takayuki、Sanada Hiroki、Uchida Akifumi、Misono Shunsuke、Sakamoto Shinichi、Komiya Akira、Ichikawa Tomohiko、Seki Naohiko
    • Journal Title

      Molecular Oncology

      Volume: 13 Issue: 9 Pages: 1898-1912

    • DOI

      10.1002/1878-0261.12532

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of pre-miR-532 (miR-532-5p and miR-532-3p) in regulation of gene expression and molecular pathogenesis in renal cell carcinoma.2019

    • Author(s)
      Yamada Y, Arai T, Kato M, Kojima S, Sakamoto S, Komiya A, Naya Y, Ichikawa T, Seki N.
    • Journal Title

      American Journal of Clinical and Experimental Urology

      Volume: 18 Pages: 11-30

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Micro-ribonucleic acid expression signature of metastatic castration-resistant prostate cancer: Regulation of NCAPH by antitumor miR-199a/b-3p2019

    • Author(s)
      Arai T, Kojima S, Yamada Y, Sugawara S, Kato M, Yamazaki K, Naya Y, Ichikawa T, Seki N.
    • Journal Title

      International journal of urology

      Volume: 26 Issue: 4 Pages: 506

    • DOI

      10.1111/iju.13911

    • URL

      https://pure.teikyo.jp/en/publications/f97e5f5d-dace-47ee-8c06-c4b9c4fcc761

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of pre-miR-532 (miR-532-5p and miR-532-3p) in regulation of gene expression and molecular pathogenesis in renal cell carcinoma.2019

    • Author(s)
      Yamada Y, Arai T, Kato M, Kojima S, Sakamoto S, Komiya A, Naya Y, Ichikawa T, Seki N
    • Journal Title

      American Journal of Clinical and Experimental Urology

      Volume: 7 Pages: 11-30

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pirin: a potential novel therapeutic target for castration-resistant prostate cancer regulated by miR-455-5p2018

    • Author(s)
      Arai Takayuki、Kojima Satoko、Yamada Yasutaka、Sugawara Sho、Kato Mayuko、Yamazaki Kazuto、Naya Yukio、Ichikawa Tomohiko、Seki Naohiko
    • Journal Title

      Molecular Oncology

      Volume: 13 Issue: 2 Pages: 322

    • DOI

      10.1002/1878-0261.12405

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular pathogenesis of renal cell carcinoma: class FormattedString { value: Impact of the anti-tumor miR-29 family on gene regulation }2018

    • Author(s)
      Yamada, Y. Sugawara, S. Arai, T. Kojima, S. Kato, M. Okato, A. Yamazaki, K. Naya, Y. Ichikawa, T. Seki, N.
    • Journal Title

      Int J Urol

      Volume: 25 Issue: 11 Pages: 953

    • DOI

      10.1111/iju.13783

    • URL

      https://localhost/en/publications/7a2668e6-2185-41ef-9dc3-1c1fe85d2edd

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impact of novel oncogenic pathways regulated by antitumor miR-451a in renal cell carcinoma2018

    • Author(s)
      Yamada Yasutaka、Arai Takayuki、Sugawara Sho、Okato Atsushi、Kato Mayuko、Kojima Satoko、Yamazaki Kazuto、Naya Yukio、Ichikawa Tomohiko、Seki Naohiko
    • Journal Title

      Cancer Sci

      Volume: 109 Issue: 4 Pages: 1239

    • DOI

      10.1111/cas.13526

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of antitumor miR-144-5p targets oncogenes: Direct regulation of syndecan-3 and its clinical significance2018

    • Author(s)
      Yamada, Y. Arai, T. Kojima, S. Sugawara, S. Kato, M. Okato, A. Yamazaki, K. Naya, Y. Ichikawa, T. Seki, N.
    • Journal Title

      Cancer Sci

      Volume: 109 Issue: 9 Pages: 2919

    • DOI

      10.1111/cas.13722

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anti-tumor roles of both strands of the miR-455 duplex: Their targets SKA1 and SKA3 are involved in the pathogenesis of renal cell carcinoma2018

    • Author(s)
      Yamada, Y. Arai, T. Kojima, S. Sugawara, S. Kato, M. Okato, A. Yamazaki, K. Naya, Y. Ichikawa, T. Seki, N.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 42 Pages: 26638

    • DOI

      10.18632/oncotarget.25410

    • URL

      https://pure.teikyo.jp/en/publications/e2f890dd-a428-4276-89e6-a2a7d33892e2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Prognostic value of novel inflammation index for patients with metastatic castration resistant prostate cancer.2020

    • Author(s)
      Yamada Y, Sakamoto S, Rii J, Yamamoto S, Kamada S, Imamura Y, Nakamura K, Komiya A, Nakatsu H, Ichikawa T.
    • Organizer
      ASCO GU 2020
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 癌抑制型microRNA-144の制御する腎癌分子ネットワークの探索.2019

    • Author(s)
      山田 康隆, 菅原 翔, 新井 隆之, 岡東 篤, 小島 聡子, 納谷 幸男, 市川 智彦, 関 直彦.
    • Organizer
      第107回日本泌尿器科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 癌抑制型マイクロRNA455-5pを起点とした去勢抵抗性前立腺癌・分子経路の探索:新規治療標的分子としてのPIRの可能性2019

    • Author(s)
      新井 隆之, 小島 聡子, 山田 康隆, 菅原 翔, 加藤 繭子, 納谷 幸男, 市川 智彦, 関 直彦
    • Organizer
      第28回泌尿器科分子・細胞研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 癌抑制型microRNA-451aの制御する腎癌分子ネットワークの探索2018

    • Author(s)
      山田 康隆, 菅原 翔, 新井 隆之, 岡東 篤, 市川 智彦, 関 直彦
    • Organizer
      日本泌尿器科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Antitumor miR-451a regulatory network is associated with poor prognosis of renal cell carcinoma2018

    • Author(s)
      Yasutaka Yamada, Takayuki Arai, Sho Sugawara, Atsushi Okato, Mayuko Kato Satoko Kojima, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki
    • Organizer
      American Association for Cancer Research
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2021-02-19  

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