| Project/Area Number |
22791280
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Osaka University |
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Principal Investigator |
TOMOKUNI Akira 大阪大学, 医学部附属病院, 医員 (40528577)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | microRNA / 抗癌剤耐性 / 網羅的発現解析 / 肝癌 / 膵癌 |
|---|
| Research Abstract |
Interferon-based(IFN-based) therapy is effective in the treatment of advanced hepatocellular carcinoma(HCC). However, the issue of resistance to this therapy remains to be solved. The aim of this study was to identify microRNAs(miRNAs) that govern the sensitivity to IFN-αin HCC cells. miRNA microarray analysis using IFN-a-resistant clones of PLC/ PRF/ 5(PLC-Rs) and their parental cells(PLC-P) was conducted. Changes in the anti-cancer effects of IFN-αwere studied after gain-of-function and loss-of-function of the candidate miRNA. miR-146a expression was significantly higher in PLC-Rs than in PLC-P. miR-146a decreased the sensitivity to IFN-a through the suppression of apoptosis. Further experiments showed that miR-146a-related resistance to IFN-a was mediated through SMAD4. The results indicated that miR-146a regulated the sensitivity of HCC cells to the cytotoxic effects of IFN-a through SMAD4, suggesting that this miRNA could be suitable for prediction of the clinical response and potential therapeutic target in HCC patients on IFN-based therapy
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