Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10802362 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2013 | 11 Pages |
Abstract
The differentiation of human peripheral blood monocytes into macrophages can be reproduced ex vivo by culturing the cells in the presence of colony-stimulating factor 1 (CSF1). Using microarray profiling to explore the role of microRNAs (miRNAs), we identified a dramatic decrease in the expression of the hematopoietic specific miR-142-3p. Up- and down-regulation of this miRNA in primary human monocytes altered CSF1-induced differentiation of monocytes, as demonstrated by changes in the expression of the cell surface markers CD16 and CD163. One of the genes whose expression is repressed by miR-142-3p encodes the transcription factor Early Growth Response 2 (Egr2). In turn, Egr2 associated with its co-repressor NGFI-A (Nerve Growth Factor-Induced gene-A) binding protein 2 (NAB2) binds to the pre-miR-142-3p promoter to negatively regulate its expression. Interestingly, the expression of miR-142-3p is abnormally low in monocytes from patients with the most proliferative forms of chronic myelomonocytic leukemia (CMML), and miR-142-3p re-expression in CMML dysplastic monocytes can improve their differentiation potential. Altogether, miR-142-3p which functions in a molecular circuitry with Egr2 is an actor of CSF1-induced differentiation of human monocytes whose expression could be altered in CMML.
Keywords
CSF1miR-142-3pNAB2SPI-1TAB2Gfi-1CMMLMafBNR3C1KLF4RTKM-CSFCUX1Egr2Rac1PI3KcAMPRas-related C3 botulinum toxin substrate 1colony-stimulating factor 1Krüppel-like factor 4Phosphatidyl Inositol 3-kinasechronic myelomonocytic leukemiamacrophage-colony stimulating factorMicroRNAMiRNAEarly growth response 2
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Authors
Brice Lagrange, Romain Z. Martin, Nathalie Droin, Romain Aucagne, Jérôme Paggetti, Anne Largeot, Raphaël Itzykson, Eric Solary, Laurent Delva, Jean-Noël Bastie,