Identification of novel CRPC therapeutics by inhibition of activated functional RNA signaling

• Project/Area Number: 15K20071
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Chiba University
• Principal Investigator: GOTO Yusuke 千葉大学, 医学部附属病院, 医員 (00710576)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 前立腺癌 / マイクロRNA / 去勢抵抗性前立腺癌

Outline of Final Research Achievements

Understanding the molecular mechanisms of the androgen-independent and metastatic signaling pathways underlying castration-resistant prostate cancer (CRPC) using current genomic approaches would help to improve therapies for and prevention of the disease. We sequenced small RNA libraries isolated from normal prostate tissue, prostate cancer (PCa) tissue and CRPC tissue. 267 miRNAs were significantly downregulated in CRPC compared with normal prostate specimen. miR-221/222 cluster was significantly downregulated in CRPC specimen. Gene expression data and in silico analysis demonstrated miR-221/222 regulated Ecm29 gene, which was highly expressed in CRPC specimen.

Research Products

• [Int'l Joint Research] University of California, San Diego/Department of Surgery(米国)
• [Int'l Joint Research] University of California, San Diego/Moores Cancer Center(米国)
• [Int'l Joint Research] カリフォルニア大学サンディエゴ校外科(米国)
• [Journal Article] Onco-GPCR signaling and dysregulated expression of microRNAs in human cancer. (2017)
  • Author(s): Nohata N, Goto Y, Gutkind JS.
  • Journal Title: J Hum Genet. Volume: 62 Issue: 1 Pages: 87-96
  • DOI: 10.1038/jhg.2016.124
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Aberrantly expressed microRNAs in bladder cancer and renal cell carcinoma. (2017)
  • Author(s): Kurozumi A, Goto Y, Okato A, Ichikawa T, Seki N.
  • Journal Title: J Hum Genet Volume: 62 Issue: 1 Pages: 49-56
  • DOI: 10.1038/jhg.2016.84
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] Regulation of E3 ubiquitin ligase-1 (WWP1) by microRNA-452 inhibits cancer cell migration and invasion in prostate cancer. (2016)
  • 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: 1135-1144
  • DOI: 10.1038/bjc.2016.95
  • 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 carcinoma. (2016)
  • 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: 59070-59086
  • DOI: 10.18632/oncotarget.10887
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Direct regulation of LAMP1 by tumor-suppressive microRNA-320a in prostate cancer. (2016)
  • 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: 111-122
  • DOI: 10.3892/ijo.2016.3522
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR-145-3p) coordinately targeted MTDH in lung squamous cell carcinoma. (2016)
  • Author(s): Mataki H, Seki N, Mizuno K, Nohata N, Kamikawaji K, Kumamoto T, Koshizuka K, Goto Y, Inoue H.
  • Journal Title: Oncotarget Volume: 7 Issue: 44 Pages: 72084-72098
  • DOI: 10.18632/oncotarget.12290
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of TPD52 by antitumor microRNA-218 suppresses cancer cell migration and invasion in lung squamous cell carcinoma. (2016)
  • Author(s): Kumamoto T, Seki N, Mataki H, Mizuno K, Kamikawaji K, Samukawa T, Koshizuka K, Goto Y, Inoue H.
  • Journal Title: Int J Oncol. Volume: 49 Issue: 5 Pages: 1870-1880
  • DOI: 10.3892/ijo.2016.3690
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of UHRF1 by dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR-145-3p): Inhibition of bladder cancer cell aggressiveness. (2016)
  • Author(s): Matsushita R, Yoshino H, Enokida H, Goto Y, Miyamoto K, Yonemori M, Inoguchi S, Nakagawa M, Seki N.
  • Journal Title: Oncotarget Volume: 7 Issue: 19 Pages: 28460-28487
  • DOI: 10.18632/oncotarget.8668
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma. (2016)
  • Author(s): Kurozumi A, Kato M, Goto Y, Matsushita R, Nishikawa R, Okato A, Fukumoto I, Ichikawa T, Seki N.
  • Journal Title: Int J Oncol Volume: in press Issue: 5 Pages: 1837-46
  • DOI: 10.3892/ijo.2016.3440
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Real-Time GFP Intravital Imaging of the Difference in Cellular and Angiogenic Behavior of Subcutaneous and Orthotopic Nude-Mouse Models of Human PC-3 Prostate Cancer. (2016)
  • Author(s): Zhang Y, Toneri M, Ma H, Yang Z, Bouvet M, Goto Y, Seki N, Hoffman RM.
  • Journal Title: J Cell Biochem. Volume: 未定 Issue: 11 Pages: 2546-2551
  • DOI: 10.1002/jcb.25547
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer. (2016)
  • Author(s): Kurozumi A, Goto Y, Matsushita R, Fukumoto I, Kato M, Nishikawa R, Sakamoto S, Enokida H, Nakagawa M, Ichikawa T, Seki N.
  • Journal Title: Cancer Sci. Volume: 107 Issue: 1 Pages: 84-94
  • DOI: 10.1111/cas.12842
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] MicroRNA expression signature of castration-resistant prostate cancer: the microRNA-221/222 cluster functions as a tumour suppressor and disease progression marker. (2015)
  • Author(s): Goto Y, Kojima S, Nishikawa R, Kurozumi A, Kato M, Enokida H, Matsushita R, Yamazaki K, Ishida Y, Nakagawa M, Naya Y, Ichikawa T, Seki N
  • Journal Title: Br J Cancer Volume: 113 Issue: 7 Pages: 1055-1065
  • DOI: 10.1038/bjc.2015.300
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MicroRNA-26a/b directly regulate La-related protein 1 and inhibit cancer cell invasion in prostate cancer. (2015)
  • Author(s): Kato M, Goto Y, Matsushita R, Kurozumi A, Fukumoto I, Nishikawa R, Sakamoto S, Enokida H, Nakagawa M, Ichikawa T, Seki N.
  • Journal Title: International Journal of Oncology Volume: 47 Issue: 2 Pages: 710-718
  • DOI: 10.3892/ijo.2015.3043
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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): Yusuke Goto, Satoko Kojima, Akira Kurozumi, Mayuko Kato, Atsushi Okato, Yukio Naya, Hideki Enokida, Ryosuke Matsushita, Masayuki Nakagawa, Tomohiko Ichikawa, Naohiko Seki
  • Organizer: American Urological Association
  • Place of Presentation: アメリカ合衆国サンディエゴ市 サンディエゴコンベンションセンター
  • Year and Date: 2016-05-06
  • Int'l Joint Research
• [Presentation] Regulation of UHRF1-mediated pathways by tumor-suppressive microRNA-101 in molecular targeted therapy resistant renal cell carcinoma. (2016)
  • Author(s): Goto Y, Kurozumi A, Kato M, Okato A, Kojima S, Matsushita R, Yoshino H, Enokida H, Nakagawa M, Naya Y, Ichikawa T, Seki N.
  • Organizer: AUA annual meeting 2016
  • Place of Presentation: アメリカ合衆国サンディエゴ市
  • Int'l Joint Research
• [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, Naya Y, Enokida H, Matsushita R, Nakagawa M, Ichikawa T, Seki N
  • Organizer: AUA annual meeting 2016
  • Place of Presentation: アメリカ合衆国サンディエゴ市
  • Int'l Joint Research
• [Presentation] 全ゲノムCRPC機能性RNA発現解析に基づくCRPC活性化分子経路の探索 (2016)
  • Author(s): 五島悠介、小島聡子、松下良介、黒住顕、加藤繭子、西川里佳、 坂本信一、榎田英樹、中川昌之、納谷幸男、市川智彦、関直彦
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
• [Presentation] 去勢抵抗性前立腺癌克服に向けた全ゲノム機能性RNA解析 (2016)
  • Author(s): 五島悠介
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Invited
• [Presentation] miR-221/222 cluster as a tumor suppressor based on microRNA expression signature of castration-resistant prostate cancer. (2015)
  • Author(s): Yusuke Goto, Satoko Kojima, Rika Nishikawa, Ryosuke Matsushita, Ichiro Fukumoto, Shinichi Sakamoto, Hideki Enokida, Masayuki Nakagawa, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki.
  • Organizer: 第74回日本癌学会総会
  • Place of Presentation: 愛知県名古屋市 名古屋国際会議場
  • Year and Date: 2015-10-06
• [Remarks] 千葉大学大学院医学研究院『先端研究部門 先端がん治療学研究講座 機能ゲノム学』
  • URL: http://genomejet.jp/
• [Remarks] 千葉大学大学院医学研究院機能ゲノム学
  • URL: http://genomejet.jp/