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.
Original language | English |
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Pages (from-to) | 1936-1946 |
Number of pages | 11 |
Journal | Biochimica et Biophysica Acta - Molecular Cell Research |
Volume | 1833 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 2013 |
Keywords
- Chronic myelomonocytic leukemia
- Egr2
- MiR-142-3p
- Molecular circuitry
- Monocyte-macrophage differentiation