2016 Fiscal Year Final Research Report
Post-transcriptional regulation of RUNX1/RUNX3 is critical for neuroblastoma cell growth or differentiation.
| Project/Area Number |
24790325
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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 |
Pathological medical chemistry
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| Research Institution | Dokkyo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2017-03-31
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| Keywords | microRNA / neuroblastoma / RUNX1 / RUNX3 / N-Myc |
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| Outline of Final Research Achievements |
The transcription factors RUNX1 and RUNX3 play pivotal roles in lineage commitment of dorsal root ganglion neurons. In neuroblastoma cell lines, protein levels of RUNX1/RUNX3 are maintained within a narrow range. The perturbation of the protein amount of RUNX1/RUNX3 results in cell death, suggesting the roles of RUNX proteins as tumor suppressors. In this study, we found that the 3’UTR (untranslated region) of both RUNX1/RUNX3 mRNA inhibited the protein translation. Several microRNAs, that are the transcription targets of N-Myc, were enriched in 3'UTR purification by the Streptavidin binding RNA aptamer. Mutagenesis reporter assay indicates that the miR18 or miR19 binding to 3’UTR contributes to translational inhibition of RUNX1 or RUNX3, respectively. N-Myc is one of most frequently amplified oncogenes in neuroblastoma and the data suggest that N-Myc could overcome tumor suppressor functions of RUNX1/RUNX3 through post-transcriptional regulation with microRNAs.
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| Free Research Field |
分子生物学
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