MicroRNA-27 enhances differentiation of myeloblasts into granulocytes by post-transcriptionally downregulating Runx1

Jue Feng, Atsushi Iwama, Masanobu Satake, Kazuyoshi Kohu

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

Abstract

Summary We investigated the regulation of the transcription factor Runx1 by microRNA (miR)-27 and the resulting effects upon the differentiation of myeloblasts into granulocytes. When 32D.cl3 cell differentiation was induced using granulocyte colony-stimulating factor (CSF3), Runx1 transcription was moderately downregulated, while Runx1 protein levels were completely inhibited, suggesting an involvement of post-transcriptional regulation. Simultaneously, levels of miR-27 and its precursor increased substantially. Reporter assays revealed that miR-27 targets the 3′UTR of the Runx1 transcript. Furthermore, introduction of pre-miR-27 alone into 32D.cl3 cells resulted in downregulation of Runx1 protein, thereby allowing the cell differentiation even in the absence of CSF3. Conversely, transduction of anti-miR-27 caused upregulation of Runx1 protein, thereby antagonizing the CSF3-mediated granulocyte differentiation. Finally, the CSF3-induced transcription factor C/EBPalpha enhanced transcription of a host gene of miR-27, C9orf3, via activation of its promoter. Thus, miR-27 enhances differentiation of myeloblasts into granulocytes via post-transcriptional downregulation of Runx1.

Original languageEnglish
Pages (from-to)412-423
Number of pages12
JournalBritish Journal of Haematology
Volume145
Issue number3
DOIs
Publication statusPublished - 2009 May 1

Keywords

  • Gene regulation
  • Granulocytes
  • MicroRNA
  • Myeloblasts
  • Runx1

ASJC Scopus subject areas

  • Hematology

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