Elucidate the functional RNA network in castration-resistant prostate cancer and therapeutic approach

• Project/Area Number: 17K11160
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Teikyo University
• Principal Investigator: Kojima Satoko 帝京大学, 医学部, 准教授 (10345019)
• Co-Investigator(Kenkyū-buntansha): 関 直彦 千葉大学, 大学院医学研究院, 准教授 (50345013)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: マイクロＲＮＡ / 去勢抵抗性前立腺癌 / 抗がん剤 / ホルモン感受性 / 癌遺伝子 / 前立腺癌 / 去勢抵抗性 / 癌抑制遺伝子 / マイクロRNA / CRPC / 機能性RNA / 転移 / 浸潤 / 次世代シークエンサー / ネットワーク / 網羅的解析

Outline of Final Research Achievements

Tumor suppressor genes induce up-regulation of oncogenes, which promote aggressiveness of castration-resistant prostate cancer (CRPC). Micro-RNAs repress expression of target genes, especially oncogenes in CRPC. To find out oncogenes which have important roles in progression of CRPC makes us possible to inhibit progression, invasion, and metastasis in CRPC. We previously reported that miR-455-5p is down-regulated in progressive PCa. We have found out the 8 possible target genes of miR-455-5p. The expression levels of Pirin was most increased in CRPC and the expression levels are repressed by miR-455-5p. miR-455-5p might a prognositic factor of progressed PCa and inhibition of expression of Pirin might be a therapeutic strategy in progressed PCa and CRPC.

Academic Significance and Societal Importance of the Research Achievements

ホルモン療法に抵抗性となった去勢抵抗性前立腺癌（CRPC）は予後が約2年から5年と予後には限りがある。前立腺癌の進展のメカニズムは色々な仮説があるが、本研究では、癌遺伝子の発現を調節するマイクロＲＮＡを同定し、その標的遺伝子を明らかにした。マイクロRNAを強発現させることで、前立腺癌の増殖や転移を抑える可能性があることから、将来的な治療への応用することができるかもしれない。

Research Products

• [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): Yasutaka Yamada,Takayuki Arai, Mayuko Kato,Satoko Kojima, Shinichi Sakamoto, Akira Komiya, Yukio Naya, Tomohiko Ichikawa, and Naohiko Seki
  • Journal Title: Am J Clin Exp Urol Volume: 7 Pages: 11-30
  • Peer Reviewed
• [Journal Article] Micro-ribonucleic acid expression signature of metastatic castration-resistant prostate cancer: Regulation of NCAPH by antitumor miR-199a/b-3p. (2019)
  • 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: 506-520
  • DOI: 10.1111/iju.13911
  • Peer Reviewed / Open Access
• [Journal Article] Pirin: a potential novel therapeutic target for castration-resistant prostate cancer regulated by miR-455-5p (2018)
  • 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: 322-337
  • DOI: 10.1002/1878-0261.12405
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular pathogenesis of renal cell carcinoma: 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(11) Issue: 11 Pages: 953-965
  • DOI: 10.1111/iju.13783
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of novel oncogenic pathways regulated by antitumor miR-451a in renal cell carcinoma (2018)
  • 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: 印刷中 Issue: 4 Pages: 1239-1253
  • DOI: 10.1111/cas.13526
  • 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 significance (2018)
  • 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 (9) Issue: 9 Pages: 2919-2936
  • DOI: 10.1111/cas.13722
  • 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 carcinoma (2018)
  • 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 (42) Issue: 42 Pages: 26638-58
  • DOI: 10.18632/oncotarget.25410
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Abiraterone acetate withdrawal syndrome: Speculations on the underlying mechanisms (2018)
  • Author(s): Kato, T. Komiya, A. Yuasa, J. Kaga, K. Kaga, M. Kojima, S. Naya, Y. Isaka, S.
  • Journal Title: Oncol Lett Volume: 15 (2) Pages: 2669-2672
  • DOI: 10.3892/ol.2017.7628
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of NCAPG by miR-99a-3p (passenger strand) inhibits cancer cell aggressiveness and is involved in CRPC (2018)
  • 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(5) Issue: 5 Pages: 1988-2002
  • DOI: 10.1002/cam4.1455
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of HMGB3 by antitumor miR-205-5p inhibits cancer cell aggressiveness and is involved in prostate cancer pathogenesis (2017)
  • 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: 195-205
  • DOI: 10.1038/s10038-017-0371-1
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of spindle and kinetochore-associated protein 1 by antitumor miR-10a-5p in renal cell carcinoma (2017)
  • 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: 2088-2101
  • DOI: 10.1111/cas.13331
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of novel miR-145-3p regulatory networks on survival in patients with castration-resistant prostate cancer (2017)
  • 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: 409-420
  • DOI: 10.1038/bjc.2017.191
  • Peer Reviewed
• [Journal Article] The roles of microRNAs in the progression of castration-resistant prostate cancer. (2017)
  • Author(s): Kojima, S. Goto, Y. Naya, Y.
  • Journal Title: J Hum Genet Volume: 62（１） Issue: 1 Pages: 25-31
  • DOI: 10.1038/jhg.2016.69
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dual strands of pre-miR-150 (miR-150-5p and miR-150-3p) act as antitumor miRNAs targeting SPOCK1 in na?ve and castration-resistant prostate cancer (2017)
  • 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: 245-256
  • DOI: 10.3892/ijo.2017.4008
  • Peer Reviewed / Open Access
• [Journal Article] Dual Strands of Pre-miR-149 Inhibit Cancer Cell Migration and Invasion through Targeting FOXM1 in Renal Cell Carcinoma (2017)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Prognostic impact of non-regional lymph node (NRLN) metastasis in bone metastatic prostate cancer (PCa) (2019)
  • Author(s): Satoko Kojima, Hiroshi Masuda, Kazuhiro Araki, Takahito Suyama, Kyokushin Hou, Kotaro Otsuka, Kousuke Mikami, Yukio Naya.
  • Organizer: 39th congress of the Societe International d’Urologie (SIU).
  • Int'l Joint Research
• [Presentation] 尿閉を契機に発見されたStageD前立腺癌に関する検討 (2019)
  • Author(s): 大塚耕太郎、小島聡子、三神功亮、芳生旭辰、巣山貴仁、荒木千裕、増田広、納谷幸男
  • Organizer: 日本泌尿器腫瘍学会第5回学術集会
• [Presentation] 癌抑制型マイクロRNA-99a-3p を起点とした去勢抵抗性前立腺癌・治療標的分子の探索 (2019)
  • Author(s): 新井隆之、小島聡子、山田康隆、菅原翔、岡東篤、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
• [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
• [Presentation] 転移性前立腺癌における遠隔リンパ節の予後因子としての重要性 (2019)
  • Author(s): 小島聡子、加藤智規、増田広、荒木千裕、巣山貴仁、芳生旭辰、大塚耕太郎、三神功亮、関根啓太、納谷幸男
  • Organizer: 第107回日本泌尿器科学会総会
• [Presentation] 間欠的内分泌療法を施行した非転移性前立腺癌のCRPCへの進展と長期予後について (2018)
  • Author(s): 小島 聡子、加藤 智規、佐藤 直秀、藤本 歩、増田 広、 荒木 千裕、巣山 貴仁、芳生 旭辰、大塚 耕太郎、 納谷 幸男
  • Organizer: 第 106 回日本泌尿器科学会総会
• [Presentation] 腎細胞癌・マイクロ RNA 発現プロファイルに基づく、機能性 RNA ネットワークの探索 (2018)
  • Author(s): 岡東 篤、新井 隆之、山田 康隆、菅原 翔、 黒住 顕、加藤 繭子、小島 聡子、納谷 幸男、 市川 智彦、関 直彦
  • Organizer: 第 106 回日本泌尿器科学会総会
• [Presentation] 癌抑制型マイクロ RNA(miR-10a-5p) が制御する治療抵抗性腎癌・新規分子ネットワークの探索 (2018)
  • Author(s): 新井 隆之、岡東 篤、小島 聡子、黒住 顕、 加藤 繭子、納谷 幸男、市川 智彦、関 直彦
  • Organizer: 第 106 回日本泌尿器科学会総会
• [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、 小島 聡子、納谷 幸男、市川 智彦、関 直彦
  • Organizer: 第 106 回日本泌尿器科学会総会
• [Presentation] 癌抑制型マイクロＲＮＡにより制御される細胞周期関連遺伝子NCAPGは、去勢知恵構成前立腺癌の治療法的分子である (2018)
  • Author(s): 新井隆之、岡東篤、山田康隆、菅原翔、黒住顕、小島聡子、納谷幸男、市川智彦、関直彦
  • Organizer: 第27回 泌尿器科分子・細胞研究会
• [Presentation] 癌抑制型microRNA-451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、小島聡子、納谷幸男、市川智彦、関直彦
  • Organizer: 第27回 泌尿器科分子・細胞研究会
• [Presentation] Antitumor miR-451a regulatory network is associated with poor prognosis of renal cell carcinoma (2018)
  • Author(s): Y. Yamada, S. Sugawara, T. Arai, A. Okato, S. Kojima, Y. Naya, T. Ichikawa, N. Seki.
  • Organizer: AACR
  • Int'l Joint Research
• [Presentation] Regulation of NCAPG by miR-99a-3p (passenger strand) inhibits cancer cell aggressiveness and is involved in CRPC (2018)
  • Author(s): T. Arai, A. Okato, Y. Yamada, S. Sugawara, A. Kurozumi, S. Kojima, Y. Naya, T. Ichikawa, N. Seki.
  • Organizer: AACR
  • Int'l Joint Research
• [Presentation] miR-452 inhibits migration and invasion of prostate cancer cells by targeting E3 ubiquitin ligase-1 (WWP1). (2017)
  • Author(s): Satoko Kojima, Yusuke Goto, Akira Kurozumi, Mayuko Kato, Atsushi Okato, Takayuki Arai, Tomohiko Ichikawa, Yukio Naya, Naohiko Seki.
  • Organizer: AACR Annual Meeting 2017
  • Int'l Joint Research
• [Presentation] Dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR-145-3p) are involved in castration-resistant prostate cancer pathogenesis. (2017)
  • Author(s): Mayuko Kato, Akira Kurozumi, Yusuke Goto, Nijiro Nohata, Takayuki Arai, Atsushi Okato, Keiichi Koshizuka, Satoko Kojima, Tomohiko Ichikawa, Naohiko Seki.
  • Organizer: AACR Annual Meeting 2017
  • Int'l Joint Research
• [Presentation] MicroRNA expression signature of patients with tyrosine kinase inhibitors failure: miR-10a-5p inhibits cancer cell aggressiveness in renal cell carcinoma. (2017)
  • Author(s): Takayuki Arai, Atsushi Okato, Akira Kurozumi, Mayuko Kato, Yusuke Goto, Keiichi Koshizuka, Satoko Kojima, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki.
  • Organizer: AACR Annual Meeting 2017
  • Int'l Joint Research
• [Presentation] Dual-strands pre-microRNA-150 (miR-150-5p and miR-150-3p) acts as tumor suppressor in prostate cancer. (2017)
  • Author(s): Atsushi Okato, Takayuki Arai, Akira Kurozumi, Mayuko Kato, Yusuke Goto, Keiichi Koshizuka, Satoko Kojima, Tomohiko Ichikawa, Naohiko Seki.
  • Organizer: AACR Annual Meeting 2017
  • Int'l Joint Research
• [Presentation] Androgen Receptor (AR) Targeted Therapy におけるTime to CRPCの重要性 (2017)
  • Author(s): 小島聡子、藤本歩、金坂学斗、芳生旭辰、巣山貴仁、荒木千裕、増田広、納谷幸男
  • Organizer: 第105回日本泌尿器科学会総会
• [Presentation] 治療抵抗性腎癌細胞で発現低下を認めるmiR-10aの機能解析と新規機能性RNA分子ネットワークの探索 (2017)
  • Author(s): 新井隆之、五島悠介、岡東篤、黒住顕、加藤繭子、小島聡子、納谷幸男、市川智彦、関直彦
  • Organizer: 第105回日本泌尿器科学会総会
• [Presentation] 癌抑制型microRNA-320aが制御する前立腺癌分子ネットワークの探索 (2017)
  • Author(s): 岡東篤、五島悠介、黒住顕、加藤繭子、新井隆之、小島聡子、市川智彦、関直彦
  • Organizer: 第105回日本泌尿器科学会総会
• [Presentation] 前立腺癌ゲノムシークエンスにより明らかとなった新規癌抑制型マイクロRNA (miR-150-5p/miR-150-3p)の機能解析 (2017)
  • Author(s): 岡東篤、五島悠介、黒住顕、加藤繭子、新井隆之、小島聡子、市川智彦、関直彦
  • Organizer: 第105回日本泌尿器科学会総会
• [Presentation] The microRNA expression signature of patients with renal cell carcinoma: Tumor suppressive miR-149-5p targeting FOXM1. (2017)
  • Author(s): Atsushi Okato, Takayuki Arai, Akira Kurozumi, Mayuko Kato, Yusuke Goto, Satoko Kojima, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki.
  • Organizer: American Urology Association 2017 in Boston
  • Int'l Joint Research
• [Presentation] Impact of microRNA expression signature of patients with TKI failure:regulation of miR-10a-5p pathways in renal cell carcinoma． (2017)
  • Author(s): Takayuki Arai, Atsushi Okato, Akira Kurozumi, Mayuko Kato, Yusuke Goto, Satoko Kojima, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki.
  • Organizer: American Urology Association 2017 in Boston
  • Int'l Joint Research
• [Presentation] Impact of antitumore microRNA-145-3p regulated RNA networks in castration-resistant prostate cancer. (2017)
  • Author(s): Akira Kurozumi, Yusuke Goto, Nijiro Nohata, Satoko Kojima, Takayuki Arai, Atsushi Okato, Mayuko Kato, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki.
  • Organizer: American Urology Association 2017 in Boston
• [Presentation] 去勢抵抗性前立腺癌治療の実際と展望～より安全に、より有効に～ (2017)
  • Author(s): 小島聡子
  • Organizer: 日本アンドロロジー学会 第36回学術大会
  • Invited
• [Presentation] 前立腺がん治療における課題と展望 ３．ホルモン療法 (2017)
  • Author(s): 小島聡子
  • Organizer: 日本泌尿器腫瘍学会第3回学術集会
  • Invited
• [Presentation] 前立腺疾患機能性RNA解析に基づく前立腺癌特異的分子ネットワークの探索 (2017)
  • Author(s): 岡東篤、小島聡子、市川智彦、関直彦
  • Organizer: 第33回前立腺シンポジウム
• [Book] Prostate Journal (2018)
  • Author(s): 小島聡子
  • Publisher: 医学図書出版株式会社
  • ISBN: 9784865172645