Clarification of microRNA functional networks and development of novel tools for diagnosis and treatment of castration-resistant prostate cancer

• Project/Area Number: 25293333
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Chiba University
• Principal Investigator: Ichikawa Tomohiko 千葉大学, 医学(系)研究科(研究院), 教授 (20241953)
• Co-Investigator(Kenkyū-buntansha): SEKI NAOHIKO 千葉大学, 大学院医学研究院, 准教授 (50345013) ; SAKAMOTO SHINICHI 千葉大学, 大学院医学研究院, 助教 (70422235)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2013: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 前立腺癌 / 癌抑制 / 転移抑制 / 去勢抵抗性 / マイクロRNA / マイクロＲＮＡ

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-221/222, miR-29s, miR-218, miR-224, miR-23b/27b/24, miR-26a/b, miR-205, and miR-223 function as tumor suppressors in prostate cancer. We have also identified the genes regulated by those miRNAs.

Research Products

• [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] 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] Validation of active surveillance criteria for pathologically insignificant prostate cancer in Asian men. (2016)
  • Author(s): Yamada Y, Sakamoto S, Sazuka T, Goto Y, Kawamura K, Imamoto T, Nihei N, Suzuki H, Akakura K, Ichikawa T.
  • Journal Title: Journal of Urology Volume: 23 Issue: 1 Pages: 49-54
  • DOI: 10.1111/iju.12952
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Low serum dehydroepiandrosterone examined by liquid chromatography-tandem mass spectrometry correlates with poor prognosis in hormone-naïve prostate cancer. (2016)
  • Author(s): Miyoshi Y, Uemura H, Umemoto S, Sakamaki K, Taguri M, Suzuki K, Shibata Y, Masumori N, Ichikawa T, Mizokami A, Sugimura Y, Nonomura N, Sakai H, Honma S, Harada M, Kubota Y.
  • Journal Title: Prostate Volume: 76 Issue: 4 Pages: 376-382
  • DOI: 10.1002/pros.23129
  • Peer Reviewed
• [Journal Article] MicroRNA-205 inhibits cancer cell migration and invasion via modulation of centromere protein F regulating pathways in prostate cancer. (2015)
  • Author(s): Nishikawa R, Goto Y, Kurozumi A, Matsushita R, Enokida H, Kojima S, Naya Y, Nakagawa M, Ichikawa T, Seki N
  • Journal Title: Int J Urol Volume: 22 Issue: 9 Pages: 867-877
  • DOI: 10.1111/iju.12829
  • Peer Reviewed / Open Access / Int'l Joint Research / 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
• [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] Up-Regulation of LAT1 during Antiandrogen Therapy Contributes to Progression in Prostate Cancer Cells (2015)
  • Author(s): Xu M, Sakamoto S, Matsushima J, Kimura T, Ueda T, Mizokami A, Kanai Y, Ichikawa T.
  • Journal Title: J Urol Volume: 195 Issue: 5 Pages: 1588-1597
  • DOI: 10.1016/j.juro.2015.11.071
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Nadir Testosterone after Long-Term Followup Predicts Prognosis in Patients with Prostate Cancer Treated with Combined Androgen Blockade. (2015)
  • Author(s): Kamada S, Sakamoto S, Ando K, Muroi A, Fuse M, Kawamura K, Imamoto T, Suzuki H, Nagata M, Nihei N, Akakura K, Ichikawa T.
  • Journal Title: Journal of Urology Volume: 194 Issue: 5 Pages: 1264-70
  • DOI: 10.1016/j.juro.2015.03.120
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Prospective evaluation of the safety of transrectal ultrasound-guided transperineal prostate biopsy based on adverse events. (2015)
  • Author(s): Namekawa T, Fukasawa S, Komaru A, Kobayashi M, Imamura Y, Ohzeki T, Takagi K, Sato Y, Akakura K, Ichikawa T, Ueda T.
  • Journal Title: Int J Clin Oncol Volume: 20 Issue: 6 Pages: 1185-1191
  • DOI: 10.1007/s10147-015-0831-6
  • Peer Reviewed
• [Journal Article] Functional significance of aberrantly expressed microRNAs in prostate cancer. (2015)
  • Author(s): Goto Y, Kurozumi A, Enokida H, Ichikawa T, Seki N.
  • Journal Title: Int J Urol Volume: 22 Issue: 3 Pages: 242-252
  • DOI: 10.1111/iju.12700
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The microRNA-23b/27b/24-1 cluster is a disease progression marker and tumor suppressor in prostate cancer. (2014)
  • Author(s): Goto Y, Kojima S, Nishikawa R, Enokida H, Chiyomaru T, Kinoshita T, Nakagawa M, Naya Y, Ichikawa T, Seki N.
  • Journal Title: Oncotarget Volume: 5 Pages: 7748-7759
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 1. Tumor-suppressive microRNA-29s inhibit cancer cell migration and invasion via (2014)
  • Author(s): Nishikawa R, Goto Y, Kojima S, Enokida H, Chiyomaru T, Kinoshita T, Sakamoto S, Fuse M, Nakagawa M, Naya Y, Ichikawa T, Seki N
  • Journal Title: Int J Oncol. Volume: 45(1) Issue: 1 Pages: 401-410
  • DOI: 10.3892/ijo.2014.2437
  • Peer Reviewed
• [Journal Article] Tumor-suppressive microRNA-218 inhibits cancer cell migration and invasion via targeting of LASP1 in prostate cancer. (2014)
  • Author(s): Nishikawa R, Goto Y, Sakamoto S, Chiyomaru T, Enokida H, Kojima S, Kinoshita T, Yamamoto N, Nakagawa M, Naya Y, Ichikawa T, Seki N.
  • Journal Title: Cancer Sci Volume: 105 Issue: 7 Pages: 802-811
  • DOI: 10.1111/cas.12441
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tumour-suppressive microRNA-224 inhibits cancer cell migration and invasion via targeting oncogenic TPD52 in prostate cancer. (2014)
  • Author(s): Goto Y, Nishikawa R, Kojima S, Chiyomaru T, Enokida H, Inoguchi S, Kinoshita T, Fuse M, Sakamoto S, Nakagawa M, Naya Y, Ichikawa T, Seki N.
  • Journal Title: FEBS Lett. Volume: 588(10) Issue: 10 Pages: 1973-1982
  • DOI: 10.1016/j.febslet.2014.04.020
  • Peer Reviewed
• [Journal Article] Usefulness of J-CAPRA Score for High-risk Prostate Cancer Patients Treated with Carbon Ion Radiotherapy Plus Androgen Deprivation Therapy. (2014)
  • Author(s): Akakura K, Tsuji H, Suzuki H, Ichikawa T, Ishikawa H, Okada T, Kamada T, Harada M, Tsujii H, Shimazaki J.
  • Journal Title: Jpn J Clin Oncol. Volume: 44 Issue: 4 Pages: 360-5
  • DOI: 10.1093/jjco/hyu006
  • Peer Reviewed / Open Access
• [Journal Article] Bone markers predict survival in castration-resistant prostate cancer patients treated with docetaxel. (2014)
  • Author(s): Endo T, Kamiya N, Suzuki H, Oka R, Lee F-C, Utsumi T, Yano M, Kamijima S, Kawamura K, Imamoto T, Ichikawa T.
  • Journal Title: World J Clin Urol Volume: 3 Issue: 2 Pages: 139-143
  • DOI: 10.5410/wjcu.v3.i2.139
  • Peer Reviewed / Open Access
• [Journal Article] High testosterone levels in prostate tissue obtained by needle biopsy correlate with poor-prognosis factors in prostate cancer patients. (2014)
  • Author(s): Miyoshi Y, Uemura H, Umemoto S, Sakamaki K, Morita S, Suzuki K, Shibata Y, Masumori N, Ichikawa T, Mizokami A, Sugimura Y, Nonomura N, Sakai H, Honma S, Harada M, Kubota Y.
  • Journal Title: BMC Cancer Volume: Sep 26 Issue: 1 Pages: 717-717
  • DOI: 10.1186/1471-2407-14-717
  • NAID: 120006986365
  • Peer Reviewed / Open Access
• [Journal Article] The tumor-suppressive microRNA-143/145 cluster inhibits cell migration and invasion by targeting GOLM1 in prostate cancer. (2014)
  • Author(s): Kojima S, Enokida H, Yoshino H, Itesako T, Chiyomaru T, Kinoshita T, Fuse M, Nishikawa R, Goto Y, Naya Y, Nakagawa M, Seki N.
  • Journal Title: J Hum Genet. Volume: 59(2) Issue: 2 Pages: 78-87
  • DOI: 10.1038/jhg.2013.121
  • Peer Reviewed
• [Journal Article] Development of nomogram to non-steroidal antiandrogen sequential alternation in prostate cancer for predictive model. (2014)
  • Author(s): Kamiya N, Suzuki H, Nishimura K, Fujii M, Okegawa T, Matsuda T, Morita T, Takihana Y, Ozono S, Namiki M, Matsubara A, Ichikawa T, Miki T.
  • Journal Title: Jpn J Clin Oncol. Volume: 44 Issue: 3 Pages: 263-269
  • DOI: 10.1093/jjco/hyt230
  • Peer Reviewed
• [Journal Article] Analysis of preoperative detection for apex prostate cancer by transrectal biopsy (2013)
  • Author(s): Sazuka T, Imamoto T, Namekawa T, Utsumi T, Yanagisawa M, Kawamura K, Kamiya N, Suzuki H, Ueda T, Ota S, Nakatani Y, Ichikawa T:
  • Journal Title: Prostate Cancer Volume: - Pages: 1-6
  • DOI: 10.1155/2013/705865
  • Peer Reviewed
• [Presentation] Targeting multiple functions of E3 ubiquitin ligase-1 (WWP1) signaling by miR-452 inhibits cancer cell migration and invasion in prostate cancer. (2015)
  • Author(s): Goto Y, Kurozumi A, Nishikawa R, Kato M, Sakamoto S, Kojima S, Naya Y Enokida H, Nakagawa M, Ichikawa T, Seki N.
  • Organizer: AUA annual meeting 2015
  • Place of Presentation: New Orleans Morial Convention Center, New Orleans, 米国 ルイジアナ州
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] Tumor suppressive microRNA-224 inhibits cancer cell migration and invasion via targeting TPD52 in prostate cancer. (2014)
  • Author(s): Goto Y, Nishikawa R, Kojima S, Sakamoto S, Kawamura K, Imamoto T, Chiyomaru T, Enokida H, Kinoshita T, Naya Y, Nakagawa M, Ichikawa T, Seki N.
  • Organizer: American Urological Association annual meeting 2014
  • Place of Presentation: 米国フロリダ州オーランド市 Orange County Convention Center
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] The functional significance and its regulated molecular targets of microRNA-23b/27b/24-1 cluster in prostate cancer. (2014)
  • Author(s): Goto Y, Nishikawa R, Kojima S, Sakamoto S, Kawamura K, Imamoto T, Chiyomaru T, Enokida H, Kinoshita T, Naya Y, Nakagawa M, Ichikawa T, Seki N.
  • Organizer: American Urological Association annual meeting 2014
  • Place of Presentation: 米国フロリダ州オーランド市 Orange County Convention Center
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Validation of active surveillance criteria for pathological insignificant prostate cancer in Japanese men. (2014)
  • Author(s): Yamada Y, Sakamoto S, Sazuka T, Goto Y, Kaga M, Yanagisawa M, Kawamura K, Kamiya N, Imamoto T, Nihei N, Suzuki H, Ichikawa T.
  • Organizer: American Urological Association annual meeting 2014
  • Place of Presentation: 米国フロリダ州オーランド市 Orange County Convention Center
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] 複数の癌抑制型microRNAによって制御されるGOLM1は前立腺癌の新規癌遺伝子である (2014)
  • Author(s): 五島悠介、西川里佳、坂本信一、千代丸 剛、榎田英樹、小島聡子、中川昌之、納谷幸男、市川智彦、関 直彦
  • Organizer: 第23回泌尿器科分子・細胞研究会
  • Place of Presentation: 山形テルサ（山形県山形市）
• [Presentation] 癌抑制型microRNAによって制御されるGOLM1は前立腺癌の新規癌遺伝子である (2014)
  • Author(s): 西川里佳、五島悠介、坂本信一、千代丸 剛、榎田英樹、小島聡子、中川昌之、納谷幸男、市川智彦、関 直彦
  • Organizer: 第23回泌尿器科分子・細胞研究会
  • Place of Presentation: 山形テルサ（山形県山形市）
• [Presentation] 前立腺癌における必須アミノ酸トランスポーターLAT1の機能解析 (2014)
  • Author(s): 徐 旻憓、坂本信一、五島悠介、西川里佳、巣山貴仁、川村幸治、今本 敬、二瓶直樹、金井好克、市川智彦
  • Organizer: 第23回泌尿器科分子・細胞研究会
  • Place of Presentation: 山形テルサ（山形県山形市）
• [Presentation] Amino Acid Transporter LAT1 is a Significant Promoter of Prostate Cnacer (2014)
  • Author(s): Sakamoto S, Xu M-H, Yamada Y, Sato H, Higuchi K, Kaga M, Yanagisawa M, Kawamura K, Imamoto T, Nihei N, Kanai Y, Ichikawa T.
  • Organizer: The 4th Congress of Asian Pacific Prostate Society
  • Place of Presentation: 万国津梁館（沖縄県名護市）
• [Presentation] Tumor suppressive microRNA-218 inhibites cancer cell migration and invasion via targeting LASP1 in prostate cancer (2014)
  • Author(s): Nishikawa R, Goto Y, Kinoshita T, Sakamoto S, Chiyomaru T, Enokida H, Kojima S, Nakagawa M, Naya Y, Ichikawa T, Seki N.
  • Organizer: AACR 2014 annual meeting
  • Place of Presentation: San Diego Convention Center (San Diego, USA)
• [Presentation] 癌抑制型microRNAが制御する前立腺癌転移機構の解明 (2013)
  • Author(s): 五島悠介、西川里佳、坂本信一、小島聡子、市川智彦、関 直彦
  • Organizer: 第29回前立腺シンポジウム
  • Place of Presentation: 東京コンファレンスセンター品川（東京都港区）
• [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/
• [Remarks] 千葉大学大学院医学研究院 泌尿器科学 教室業績一覧 2013年度
  • URL: http://www.m.chiba-u.ac.jp/class/urology/