Elucidation of molecular pathway of benign prostatic hyperplasia and prostate cancer based on microRNA.
Project/Area Number |
18K16685
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56030:Urology-related
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Research Institution | Chiba University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 前立腺癌 / 前立腺肥大症 / マイクロRNA / 去勢抵抗性前立腺癌 / エクソソーム / 治療抵抗性 / microRNA |
Outline of Final Research Achievements |
miRNA expression signatures by RNA sequencing showed that the miR-455-duplex (miR-455-5p and miR-455-3p) acted as antitumor miRNAs in prostate cancer(PCa) cells. Based on a large patient cohort in The Cancer Genome Atlas, expression of eight miR-455-5p/-3p target genes (PIR: P = 0.0137, LRP8: P = 0.0495, IGFBP3: P = 0.0172, DMBX1: P = 0.0175, CCDC64: P = 0.0446, TUBB1: P = 0.0149, KIF21B: P = 0.0336, and NFAM1: P = 0.0013) was significantly associated with poor prognosis of PCa patients. Here, we focused on PIR (pirin), a highly conserved member of the cupin superfamily. PIR expression was directly regulated by miR-455-5p, and PIR overexpression was detected in hormone-sensitive prostate cancer (HSPC) surgical specimens and CRPC autopsy specimens. Loss-of-function assays using siRNA or an inhibitor (bisamide) showed that downregulation of PIR expression blocked cancer cell migration and invasion. PIR might be a promising diagnostic marker and therapeutic target for HSPC and CRPC.
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Academic Significance and Societal Importance of the Research Achievements |
本研究期間中に我々は、新規癌抑制型マイクロRNAを起点とした機能性RNA分子ネットワーク解析を行い、治療抵抗性前立腺癌における新規治療標的分子を探索した。これまでの治療抵抗性前立腺癌における治療の中心として、アンドロゲン受容体を標的としたより強力な抗アンドロゲン剤であったが、本研究結果から得られた候補分子は既存の治療とは異なる経路を標的とするものであり、新たな治療戦略としての可能性を示したといえる。ホルモン依存性の癌である前立腺癌において、アンドロゲン非依存性に増殖能を獲得した治療抵抗性前立腺癌に対する新規治療法の開発は、罹患数の増加が顕著な前立腺癌治療において非常に意義の大きいものである。
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Report
(3 results)
Research Products
(15 results)
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[Journal Article] Molecular pathogenesis of renal cell carcinoma: Impact of the anti-tumor miR-29 family on gene regulation2018
Author(s)
Yamada, Y. Sugawara, S. Arai, T. Kojima, S. Kato, M. Okato, A. Yamazaki, K. Naya, Y. Ichikawa, T. Seki, N.
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Journal Title
Int J Urol
Volume: 25(11)
Issue: 11
Pages: 953-965
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Cancer Sci
Volume: 109 (9)
Issue: 9
Pages: 2919-2936
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Oncotarget
Volume: 9 (42)
Issue: 42
Pages: 26638-58
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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