| Project/Area Number |
23659192
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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 |
Human pathology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
|
| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 脂肪肉腫 / 染色体転座 / TLS-CHOP 遺伝子 / iPS 細胞 / 粘液型脂肪肉腫 / TLS-CHOP / 染色体リプログラミング / miRNA / TLS/FUS-CHOP遺伝子 / iPS細胞 |
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| Research Abstract |
Myxoid liposarcomas (MLSs) are characterized by t(12;16)(q13;p11) translocation and expression of TLS-CHOP chimeric oncoprotein. In this study, we have found that miR-486 regulate differentiation of adipocyte. Furthermore, miR-486 expression was repressed in TLS-CHOP-expressed NIH3T3 fibroblasts and MLS tissues, and exogenous overexpression of miR-486 repressed growth of MLS cells. In addition, we have identified plasminogen activator inhibitor-1 (PAI-1) as a novel target gene of miR-486. Furthermore, knockdown of PAI-1 by a specific small interfering RNA (siRNA) inhibited growth of MLS cells, suggesting that increased expression of PAI-1 by miR-486 repression is critical for survival of MLS cells. Collectively, these results suggest a novel essential molecular mechanism that TLS-CHOP activates PAI-1 expression by repression of miR-486 expression in MLS tumorigenesis and development.
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