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MicroRNA‐27 enhances differentiation of myeloblasts into granulocytes by post‐transcriptionally downregulating Runx1
Author(s) -
Feng Jue,
Iwama Atsushi,
Satake Masanobu,
Kohu Kazuyoshi
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.07632.x
Subject(s) - runx1 , downregulation and upregulation , transcription factor , biology , microrna , transcription (linguistics) , cellular differentiation , microbiology and biotechnology , cancer research , gene , genetics , linguistics , philosophy
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.