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Post-transcriptional regulation of RUNX1/RUNX3 is critical for neuroblastoma cell growth or differentiation.

Research Project

Project/Area Number 24790325
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionDokkyo Medical University

Principal Investigator

INOUE Ken-ichi  獨協医科大学, 医学部, 准教授 (90587974)

Project Period (FY) 2012-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsmicroRNA / neuroblastoma / RUNX1 / RUNX3 / N-Myc / microRNAクローニング / 次世代シーケンサー / ストレプトアビジンアプタマー / 神経芽腫 / RUNX転写因子
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.

Report

(6 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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