Functional analyses of oncogenic microRNA by genome editing and development of innovative genome-based drug discovery for bladder cancer.
| Project/Area Number |
17H04332
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kagoshima University |
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Principal Investigator |
ENOKIDA Hideki 鹿児島大学, 医歯学域医学系, 准教授 (80347103)
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| Co-Investigator(Kenkyū-buntansha) |
中川 昌之 鹿児島大学, 医歯学域医学系, 教授 (90164144)
吉野 裕史 鹿児島大学, 医歯学域鹿児島大学病院, 助教 (90642611)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | マイクロRNA / 膀胱癌 / 癌遺伝子 / miRNA 223 / WDR62 / 膀胱がん / ゲノム編集 / ゲノム編集技術 |
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| Outline of Final Research Achievements |
Based on the microRNA expression analyses by next generation sequencing, Patients with high expression of miR-199 family showed poorer prognosis compared to the counter pert. The mirs function as tumor suppressive miRNA via suppressing Integrin signals. On the other hand, miR-223 transfection to bladder cancer cell lines showed inhibitions of cell proliferation, migration, and invasion as well as inducing cell apoptosis. Furthermore, Sarilasib, an antagonist to HRAS showed inhibitions of cell proliferation, migration, and invasion with or without HRAS mutations. We also found that the patients with high expression of PHGDH gene involved in Serine synthesis pathway had poorer prognosis, and it was associated with Gemcitabine and cisplatin chemo-resistance in patients with bladder cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の成果でマイクロRNAを基点とした膀胱癌の増殖/転移に関わるいくつかの重要な分子経路が明らかになった。その経路を遮断する治療薬候補も同定出来て画期的であった。さらに他の治療薬の開発に繋がるため、次の段階への大きな礎となりうる。本研究の成功は、現在、有効な治療法の少ない進行性膀胱癌患者に対して大きな福音をもたらすと思われる。
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Report
(4 results)
Research Products
(6 results)
