| Project/Area Number |
15K10697
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Hokkaido University |
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Principal Investigator |
DONG PEIXIN 北海道大学, 医学研究院, 助教 (50602504)
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| Co-Investigator(Kenkyū-buntansha) |
櫻木 範明 北海道大学, 医学研究院, 特任教授 (70153963)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 子宮頸癌 / microRNA / EMT / 癌幹細胞 / p53 / iASPP / 癌 / 遺伝子 |
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| Outline of Final Research Achievements |
Derepression of wild-type p53 by suppressing its negative inhibitor iASPP represents a potential therapeutic option for cervical cancer. We investigated whether targeting iASPP can restore p53 tumor suppressor functions and how epigenetic mechanisms, such as aberrant microRNA (miRNA) expression, regulate iASPP expression in this cancer. We found that iASPP acts as a key promoter of CC cell proliferation, EMT, invasion and cancer stemness, by interacting with p53 to suppress p53-mediated transcription of target genes and to reduce p53-responsive microRNA-34a levels. microRNA-124 directly targets iASPP to reduce the expression of iASPP and attenuate cervical cancer cell growth and invasiveness. iASPP also promotes EMT and confers cisplatin resistance in cervical cancer via p53-miR-20a-FBXL5/BTG3 signaling. Altogether, reducing iASPP expression leads to p53-dependent tumor suppression, suggesting a therapeutic strategy to treat iASPP-associated cervical cancer.
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