2015 Fiscal Year Final Research Report
Investigation of miRNA targeting Notch1
| Project/Area Number |
26830115
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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 |
Tumor therapeutics
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| Research Institution | Tokai University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Keywords | T-ALL / Notch1 / miRNA |
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| Outline of Final Research Achievements |
Notch1 mutation is one of the most frequent mutation found in T-ALL. miRNA is non-coding RNA regulating target genes post-transcriptionally. Recently miRNAs are suggested as potential biologics. In this study, I investigated miRNA targeting Notch1.
Focusing on the function of Notch receptors as adhesion molecules, I established a screening system for miRNA targeting Notch1. Library of murine miRNAs was transduced into T-ALL-derived MOLT-4, and MOLT-4 cells were incubated on OP9 expressing Notch ligand, Dll4. If transduced miRNA represses Notch1 in MOLT-4, it is suggested the adhesion of MOLT4 to Dll4 would be interfered. By use of this system, I obtained 5 candidate miRNAs. One of them, miR-669m-1 functionally suppressed Notch1 in vitro. Next I performed bone-marrow transfer experiments, and found that miR-669m-1 expressing LSK cells efficiently gave rise to B cells. Since Notch1 suppresses B-lymphopoiesis, miR-669m-1 was suggested to enhance B cell development by repressing Notch1.
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| Free Research Field |
血液学
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