MicroRNA-27 enhances differentiation of myeloblasts into granulocytes by post-transcriptionally downregulating Runx1.
Br J Haematol
; 145(3): 412-23, 2009 May.
Article
em En
| MEDLINE
| ID: mdl-19298589
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regiões 3' não Traduzidas
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MicroRNAs
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Interferência de RNA
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Células Precursoras de Granulócitos
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Subunidade alfa 2 de Fator de Ligação ao Core
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Granulócitos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Br J Haematol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão