Identifying molecular pathogenesis of advanced renal cell carcinoma based on microRNA expression

• Project/Area Number: 17K16778
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Chiba University
• Principal Investigator: Okato Atsushi 千葉大学, 医学部附属病院, 医員 (90756719)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: マイクロRNA / 治療抵抗性腎癌 / 腎細胞癌

Outline of Final Research Achievements

In recent years, although the development of new therapeutic agents for the advanced renal cell carcinoma have progressed, its effects are limited, and it is considered that elucidation of molecular pathways for acquiring treatment resistance is indispensable.
We generated a "treatment resistant renal cell carcinoma microRNA expression profile" from autopsy specimens after molecular targeted therapeutic agent treatment and identified microRNAs whose expressions are altered in cancerous tissue. As a result of searching for molecular networks controlled by these microRNAs, genes involved in cancer metastasis were identified. Genes targeted by these microRNAs have been confirmed to be a prognostic factor in renal cell carcinoma from the database of TCGA (the cancer genome atlas).

Academic Significance and Societal Importance of the Research Achievements

近年開発された分子標的治療薬は、進行腎細胞癌に対しても一定の治療効果を上げているが、治療経過中に抵抗性を獲得することが多く、その分子経路は十分に解明されていない。我々は分子標的治療薬治療後の剖検検体から、「治療抵抗性腎細胞癌マイクロRNA発現プロファイル」を作成し、癌組織で発現が抑制されているマイクロRNAの探索を行った。これらマイクロRNAが制御する分子ネットワークを探索した結果、癌の転移に関与する遺伝子を同定した。これらの遺伝子を標的とした治療薬の開発することは、新たな治療薬の開発の一助となると思われる。

Research Products

• [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] Molecular pathogenesis of interstitial cystitis based on microRNA expression signature: miR-320 family-regulated molecular pathways and targets. (2018)
  • 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: 印刷中 Issue: 5 Pages: 543-554
  • DOI: 10.1038/s10038-018-0419-x
  • 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 pathogenesis (2018)
  • 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
  • Peer Reviewed
• [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 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] 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] Antitumor miR-150-5p and miR-150-3p inhibit cancer cell aggressiveness by targeting SPOCK1 in head and neck squamous cell carcinoma. (2017)
  • Author(s): Koshizuka, K., T. Hanazawa, N. Kikkawa, K. Katada, A. Okato, T. Arai, T. Idichi, Y. Osako, Y. Okamoto and N. Seki
  • Journal Title: Auris Nasus Larynx Volume: - Issue: 4 Pages: 854-865
  • DOI: 10.1016/j.anl.2017.11.019
  • 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
• [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
• [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
  • Organizer: 第106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): Okato Atsushi
  • Organizer: 2017 AUA Annual Meeting
  • Int'l Joint Research
• [Remarks] 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/