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MicroRNA-27 enhances differentiation of myeloblasts into granulocytes by post-transcriptionally downregulating Runx1.
- Source :
-
British journal of haematology [Br J Haematol] 2009 May; Vol. 145 (3), pp. 412-23. Date of Electronic Publication: 2009 Mar 02. - Publication Year :
- 2009
-
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.
- Subjects :
- Animals
Cell Differentiation physiology
Cell Line
Core Binding Factor Alpha 2 Subunit analysis
Core Binding Factor Alpha 2 Subunit metabolism
Electroporation
Gene Expression
Gene Expression Regulation
HeLa Cells
Humans
Immunoblotting
Luciferases, Firefly genetics
Mice
MicroRNAs genetics
Promoter Regions, Genetic
RNA, Small Interfering pharmacology
Receptors, Colony-Stimulating Factor genetics
Receptors, Colony-Stimulating Factor metabolism
Transfection methods
3' Untranslated Regions
Core Binding Factor Alpha 2 Subunit genetics
Granulocyte Precursor Cells physiology
Granulocytes physiology
MicroRNAs metabolism
RNA Interference
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2141
- Volume :
- 145
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- British journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 19298589
- Full Text :
- https://doi.org/10.1111/j.1365-2141.2009.07632.x