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Elucidation of the microRNA-mediated RNA networks in castration resistant prostate cancer and development of innovative treatments

Research Project

Project/Area Number 16H05462
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionChiba University

Principal Investigator

Ichikawa Tomohiko  千葉大学, 大学院医学研究院, 教授 (20241953)

Co-Investigator(Kenkyū-buntansha) 関 直彦  千葉大学, 大学院医学研究院, 准教授 (50345013)
坂本 信一  千葉大学, 医学部附属病院, 講師 (70422235)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords前立腺癌 / 癌抑制 / 転移抑制 / 去勢抵抗性 / マイクロRNA / 泌尿器癌 / microRNA / マイクロRNA / microRNA
Outline of Final Research Achievements

We constructed the microRNA (miRNA) expression signature of castration-resistant prostate cancer (CRPC) using clinical specimens, and investigated the functional significance of tumor-suppressive miRNAs. We further investigated oncogenes regulated by the tumor-suppressive miRNAs. We have revealed that miR-452, miR-320a, miR-26a/b, miR-29a/b/c, miR-218, miR-145-3p, miR-150-5p/3p, miR-205-5p, miR-99a-3p, miR-455-5p/3p, and miR-199a/b-3p function as tumor suppressors in prostate cancer. We have also identified the genes regulated by those miRNAs.

Academic Significance and Societal Importance of the Research Achievements

前立腺癌で発現異常を認めるマイクロRNAの機能性RNA分子ネットワークの解析を行うことにより、前立腺癌やCRPCの機能性RNA分子ネットワークの解析を進める事ができた。それらが制御する癌遺伝子は前立腺癌の予後を予測することが可能な分子マーカーであった。これにより、前立腺癌の診療、特に去勢抵抗性前立腺癌の診断や治療への道筋をつけることができた。今後の研究の展開により新規治療法を確立するための基盤を整えることができた。

Report

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

    (29 results)

All 2019 2018 2017 2016 Other

All Journal Article (27 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 27 results,  Open Access: 20 results,  Acknowledgement Compliant: 5 results) Presentation (1 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [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
      2018 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: 7 Pages: 11-30

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of NCAPG by miR-99a-3p (passenger strand) inhibits cancer cell aggressiveness and is involved in CRPC2018

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

      Cancer Med

      Volume: 7 Issue: 5 Pages: 1988

    • DOI

      10.1002/cam4.1455

    • URL

      https://pure.teikyo.jp/en/publications/7c3730f9-3e0f-4bd0-853e-030df1b20a4e

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of bone scan index in the prognosis and effects of therapy on prostate cancer with bone metastasis: Study design and rationale for the multicenter Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index (PROSTAT-BSI) study2018

    • Author(s)
      Nakajima Kenichi、Kaneko Go、Takahashi Satoru、Matsuyama Hideyasu、Shiina Hiroaki、Ichikawa Tomohiko、Horikoshi Hiroyuki、Hashine Katsuyoshi、Sugiyama Yutaka、Miyao Takeshi、Kamiyama Manabu、Harada Kenichi、Ito Akito、Mizokami Atsushi、the PROSTAT-BSI Investigators
    • Journal Title

      International Journal of Urology

      Volume: 25 Issue: 5 Pages: 492-499

    • DOI

      10.1111/iju.13556

    • NAID

      120006471063

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment strategy for metastatic prostate cancer with extremely high PSA level: reconsidering the value of vintage therapy2018

    • Author(s)
      Sakamoto Shinichi、Yamada Yasutaka、Amiya Yoshiyasu、Sasaki Makoto、Shima Takayuki、Komiya Akira、Suzuki Noriyuki、Akakura Koichiro、Ichikawa Tomohiko、Nakatsu Hiroomi
    • Journal Title

      Asian Journal of Andrology

      Volume: 20 Issue: 5 Pages: 432-432

    • DOI

      10.4103/aja.aja_24_18

    • Related Report
      2018 Annual Research 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 Annual Research 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 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Duration of androgen deprivation therapy and nadir of testosterone at 20 ng/dL predict testosterone recovery to supracastrate level in prostate cancer patients who received external beam radiotherapy.2018

    • Author(s)
      Takei A, Sakamoto S, Wakai K, Tamura T, Imamura Y, Xu M, Maimaiti M, Kawamura K, Imamoto T, Komiya A, Akakura K, Ichikawa T.
    • Journal Title

      Int J Urol.

      Volume: 25 Issue: 4 Pages: 352-358

    • DOI

      10.1111/iju.13521

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Biparametric Prostate Imaging, the Reporting and Data System, Version 2, and International Society of Urological Pathology Grade Predict for Biochemical Recurrence After Radical Prostatectomy.2018

    • Author(s)
      Takeuchi N, Sakamoto S, Nishiyama A, Horikoshi T, Yamada Y, Iizuka J, Maimaiti M, Imamura Y, Kawamura K, Imamoto T, Komiya A, Ikehara Y, Akakura K, Ichikawa T.
    • Journal Title

      Clin Genitourin Cancer

      Volume: 「印刷中」 Issue: 4 Pages: e817-e829

    • DOI

      10.1016/j.clgc.2018.02.011

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / 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
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular pathogenesis of interstitial cystitis based on microRNA expression signature: MiR-320 family-regulated molecular pathways and targets2018

    • Author(s)
      Arai T, Fuse M, Goto Y, Kaga K, Kurozumi A, Yamada Y, Sugawara S, Okato A, Ichikawa T, Yamanishi T, Seki N.
    • Journal Title

      Journal of Human Genetics

      Volume: 63 Issue: 5 Pages: 543

    • DOI

      10.1038/s10038-018-0419-x

    • URL

      https://pure.teikyo.jp/en/publications/ba001722-4ea5-405b-b358-cefc9a4a29d7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual strands of the miR-223 duplex (miR-223-5p and miR-223-3p) inhibit cancer cell aggressiveness: targeted genes are involved in bladder cancer pathogenesis2018

    • Author(s)
      Sugawara Sho、Yamada Yasutaka、Arai Takayuki、Okato Atsushi、Idichi Tetsuya、Kato Mayuko、Koshizuka Keiichi、Ichikawa Tomohiko、Seki Naohiko
    • Journal Title

      J Hum Genet

      Volume: 印刷中 Issue: 5 Pages: 657-668

    • DOI

      10.1038/s10038-018-0437-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual strands of pre-miR-150 (miR-150-5p and miR-150-3p) act as antitumor miRNAs targeting SPOCK1 in naïve and castration-resistant prostate cancer2017

    • Author(s)
      Okato Atsushi、Arai Takayuki、Kojima Satoko、Koshizuka Keiichi、Osako Yusaku、Idichi Tetsuya、Kurozumi Akira、Goto Yusuke、Kato Mayuko、Naya Yukio、Ichikawa Tomohiko、Seki Naohiko
    • Journal Title

      International Journal of Oncology

      Volume: 51 Issue: 1 Pages: 245

    • DOI

      10.3892/ijo.2017.4008

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of novel miR-145-3p regulatory networks on survival in patients with castration-resistant prostate cancer2017

    • Author(s)
      Goto Yusuke、Kurozumi Akira、Arai Takayuki、Nohata Nijiro、Kojima Satoko、Okato Atsushi、Kato Mayuko、Yamazaki Kazuto、Ishida Yasuo、Naya Yukio、Ichikawa Tomohiko、Seki Naohiko
    • Journal Title

      British Journal of Cancer

      Volume: 117 Issue: 3 Pages: 409

    • DOI

      10.1038/bjc.2017.191

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of HMGB3 by antitumor miR-205-5p inhibits cancer cell aggressiveness and is involved in prostate cancer pathogenesis2017

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

      J Hum Genet

      Volume: 63 Issue: 2 Pages: 195

    • DOI

      10.1038/s10038-017-0371-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Testosterone Reduction of 480 ng/dL Predicts Favorable Prognosis of Japanese Men With Advanced Prostate Cancer Treated With Androgen-Deprivation Therapy.2017

    • Author(s)
      Yamamoto S, Sakamoto S, Minhui X, Tamura T, Otsuka K, Sato K, Maimaiti M, Kamada S, Takei A, Fuse M, Kawamura K, Imamoto T, Komiya A, Akakura K, Ichikawa T.
    • Journal Title

      Clin Genitourin Cancer

      Volume: 15 Issue: 6 Pages: e1107-e1115

    • DOI

      10.1016/j.clgc.2017.07.023

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cancer-specific mortality of high-risk prostate cancer after carbon-ion radiotherapy plus long-term androgen deprivation therapy2017

    • Author(s)
      Kasuya Goro、Ishikawa Hitoshi、Tsuji Hiroshi、Haruyama Yasuo、Kobashi Gen、Ebner Daniel K.、Akakura Koichiro、Suzuki Hiroyoshi、Ichikawa Tomohiko、Shimazaki Jun、Makishima Hirokazu、Nomiya Takuma、Kamada Tadashi、Tsujii Hirohiko、the Working Group for Genitourinary Tumors
    • Journal Title

      Cancer Science

      Volume: 108 Issue: 12 Pages: 2422-2429

    • DOI

      10.1111/cas.13402

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significant prognostic difference between Grade Group 4 and 5 in the 2014 International Society of Urological Pathology Grading System for High Grade Prostate Cancer with Bone Metastasis2017

    • Author(s)
      Yamada Yasutaka、Sakamoto Shinichi、Shimazaki Jun、Sugiura Masahiro、Amiya Yoshiyasu、Sasaki Makoto、Shima Takayuki、Komiya Akira、Suzuki Noriyuki、Akakura Koichiro、Ichikawa Tomohiko、Nakatsu Hiroomi
    • Journal Title

      Prostate Int

      Volume: 5 Issue: 4 Pages: 143-148

    • DOI

      10.1016/j.prnil.2017.03.001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of spindle and kinetochore-associated protein 1 by antitumor miR-10a-5p in renal cell carcinoma2017

    • Author(s)
      Arai Takayuki、Okato Atsushi、Kojima Satoko、Idichi Tetsuya、Koshizuka Keiichi、Kurozumi Akira、Kato Mayuko、Yamazaki Kazuto、Ishida Yasuo、Naya Yukio、Ichikawa Tomohiko、Seki Naohiko
    • Journal Title

      Cancer Science

      Volume: 108 Issue: 10 Pages: 2088

    • DOI

      10.1111/cas.13331

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dual strands of Pre-miR-149 inhibit cancer cell migration and invasion through targeting FOXM1 in renal cell carcinoma2017

    • Author(s)
      Okato Atsushi、Arai Takayuki、Yamada Yasutaka、Sugawara Sho、Koshizuka Keiichi、Fujimura Lisa、Kurozumi Akira、Kato Mayuko、Kojima Satoko、Naya Yukio、Ichikawa Tomohiko、Seki Naohiko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 18 Issue: 9 Pages: 1969-1969

    • DOI

      10.3390/ijms18091969

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of metastasis-promoting LOXL2 gene expression by antitumor microRNAs in prostate cancer2017

    • Author(s)
      Kato M, Kurozumi A, Goto Y, Matsushita R, Okato A, Nishikawa R, Fukumoto I, Koshizuka K, Ichikawa T, Seki N.
    • Journal Title

      J Hum Genet

      Volume: 62 Issue: 1 Pages: 123

    • DOI

      10.1038/jhg.2016.68

    • NAID

      40021036352

    • URL

      https://pure.teikyo.jp/en/publications/9445c673-acd3-4c99-8eca-fb2a8f9d8dc2

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Aberrantly expressed microRNAs in bladder cancer and renal cell carcinoma2017

    • Author(s)
      Kurozumi A, Goto Y, Okato A, Ichikawa T, Seki N.
    • Journal Title

      J Hum Genet

      Volume: 62 Issue: 1 Pages: 49

    • DOI

      10.1038/jhg.2016.84

    • URL

      https://pure.teikyo.jp/en/publications/7905ff57-984e-4066-a590-1cb945e568eb

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Regulation of E3 ubiquitin ligase-1 (WWP1) by microRNA-452 inhibits cancer cell migration and invasion in prostate cancer2016

    • Author(s)
      Goto Y, Kojima S, Kurozumi A, Kato M, Okato A, Matsushita R, Ichikawa T, Seki N.
    • Journal Title

      Br J Cancer

      Volume: 114 Issue: 10 Pages: 1135

    • DOI

      10.1038/bjc.2016.95

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Direct regulation of LAMP1 by tumor-suppressive microRNA-320a in prostate cancer2016

    • Author(s)
      Okato A, Goto Y, Kurozumi A, Kato M, Kojima S, Matsushita R, Yonemori M, Miyamoto K, Ichikawa T, Seki N.
    • Journal Title

      Int J Oncol

      Volume: 49 Issue: 1 Pages: 111

    • DOI

      10.3892/ijo.2016.3522

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The microRNA signature of patients with sunitinib failure: Regulation of UHRF1 pathways by microRNA-101 in renal cell carcinoma2016

    • Author(s)
      Goto Y, Kurozumi A, Nohata N, Kojima S, Matsushita R, Yoshino H, Yamazaki K, Ishida Y, Ichikawa T, Naya Y, Seki N.
    • Journal Title

      Oncotarget

      Volume: 7 Issue: 37 Pages: 59070

    • DOI

      10.18632/oncotarget.10887

    • URL

      https://pure.teikyo.jp/en/publications/c3fc2cc9-a524-4a56-b73c-fd643ab15d71

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Identification of dual tumor-suppressors (miR-222-5p/miR-222-3p) based on microRNA expression signature by deep sequencing of CRPC.2016

    • Author(s)
      Goto Y, Kojima S, Kurozumi A, Kato M, Okato A, Sakamoto S, Naya Y, Enokida H, Matsushita R, Nakagawa M, Ichikawa T, Seki N.
    • Organizer
      AUA annual meeting 2016
    • Place of Presentation
      San Diego Convention Center, San Diego, 米国 カリフォルニア州
    • Year and Date
      2016-05-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 千葉大学大学院医学研究院泌尿器科学

    • URL

      http://www.m.chiba-u.ac.jp/class/urology/

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report 2016 Annual Research Report

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

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