| Project/Area Number |
17K16555
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Digestive surgery
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| Research Institution | Kobe University |
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Principal Investigator |
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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 |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 大腸癌 / マイクロRNA / miR-221 / RNA結合蛋白 / QKI / 癌幹細胞 / シークエンス解析 / QKI5 |
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| Outline of Final Research Achievements |
In this study, we identified miR-221 was highly expressed in cancer stem cell population in colon cancer tissue. High levels of miR-221 expression reduced survival in CRC patients. miR-221 enhanced organoid-forming capacity of both conventional CRC cell lines and patient-derived xenografts (PDXs) in vitro. Importantly, constitutive downregulation of miR-221 suppressed organoid-forming capacity in vitro and substantially reduced the tumorigenic capacity of CSC populations from PDX lines in vivo. Finally, QKI-5, was identified as a functional targets of miR-221. As expected, overexpression of QKI-5 suppressed organoid-forming capacity in vitro and tumorigenic capacity of CRC PDX cells in vivo. Our study reveals a mechanistic link between miR-221 and QKI, and highlights their key role in regulating CSC properties in human colorectal cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、大腸癌組織中の大腸癌幹細胞のマイクロRNAプロファイルを世界に先駆け明らかにした。また、大腸癌幹細胞でマイクロRNA-221の発現が選択的に上昇していることを発見し、マイクロRNA-221が大腸癌の幹細胞性を制御する機能をもつことを解明した。さらに、マイクロRNA-221の標的遺伝子としてRNA結合蛋白質QKI-5を同定した。本研究の成果は、マイクロRNA-221の抑制による癌幹細胞を標的とした治療薬の開発への応用が期待できる。
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