| Project/Area Number |
25670078
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Kyushu University |
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Principal Investigator |
IEIRI Ichiro 九州大学, 薬学研究科(研究院), 教授 (60253473)
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| Co-Investigator(Kenkyū-buntansha) |
HIROTA Takeshi 九州大学, 薬学研究院・薬物動態学分野, 助教 (80423573)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | microRNA / P-gp / miRNA / p-糖タンパク質 / 転写制御 / 抗がん剤 / 耐性克服 |
|---|
| Outline of Final Research Achievements |
P-glycoprotein (P-gp, ABCB1) is one of the best studied ATP-binding cassette transporters. Over-expressed P-gp in cancer tissues confers resistance to a broad range of anticancer drugs. It is important to clarify the regulation mechanism of ABCB1 gene expression. MicroRNA regulates the target genes expression negatively through translational repression or mRNA degradation. We had already shown that ABCB1 is the target of miR-27a. In this study, we analyzed the mechanism behind the regulation of P-gp expression by of miR-27a regulating P-gp expression and evaluated the effect of miR-27a on the sensitivity to anti-cancer drug in human cell lines. Our results suggest that miRr-27a increased the expression of ABCB1 mRNA via down-regulated HIPK2 expression in Caco2 cells. Precursor miR-27a transfected Caco2 cells showed the decreased the sensitivity to irinotecan and doxorubicin. Regulating miR-27a expression levels may allow the application of individualized cancer chemotherapy.
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