A role for miR-142-3p in colony-stimulating factor 1-induced monocyte differentiation into macrophages

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.

miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis

“…Hematopoietic-specific miR-142 has emerged in recent years as a critical regulator of various blood and lymphoid cell lineages (Gauwerky et al, 1989; Chen et al, 2004; Huang et al, 2009; Belz, 2013; Lagrange et al, 2013; Lu et al, 2013; Mildner et al, 2013; Nimmo et al, 2013; Sonda et al, 2013; Sun et al, 2013; Zhou et al, 2013). Our analysis unveils the critical functions of miR-142 in the MK lineage.…”

“…Pioneering experimental evidence has suggested miR-142 involvement in lymphocyte differentiation (Chen et al, 2004) and recently, miR-142 was also shown to play a role in the specification of definitive hemangioblasts (Lu et al, 2013; Nimmo et al, 2013), and in lymphoid and myeloid lineages (Gauwerky et al, 1989; Chen et al, 2004; Huang et al, 2009; Belz, 2013; Lagrange et al, 2013; Lu et al, 2013; Nimmo et al, 2013; Sonda et al, 2013; Sun et al, 2013; Zhou et al, 2013). Furthermore, miR-142 is involved in the compound immune response to North American eastern equine encephalitis virus (Trobaugh et al, 2014) and our work uncovered a key role for miR-142 in the maintenance of CD4 + dendritic cells (Mildner et al, 2013).…”

MicroRNA-142-3p Induces Atherosclerosis-Associated Endothelial Cell Apoptosis by Directly Targeting Rictor

“…Over the years, miR-142-3p has gained considerable attention for its quintessential role in regulating the function of immune cells [44]. The study done by Lagrange et al identified the contribution of miR-142-3p to CSF1-induced differentiation of human monocytes into macrophages and demonstrated that this miRNA is part of a molecular circuitry involved the transcription factor Egr2 [45]. MiR-142-3p plays a critical role in modulating age-associated dysfunction of macrophages and LPS-induced dendritic cells responses and mortality via targeting IL-6 [46,47].…”

Alphaviruses suppress host immunity by preventing myeloid cell replication and antagonizing innate immune responses

“…Hematopoietic cells (e.g. monocytes, macrophages, dendritic cells, granulocytes) express miR-142-3p, a microRNA (miRNA) required for maintaining dendritic cell homeostasis [22], regulating IL-6 production [23], and regulating macrophage differentiation [24,25]. After virus entry, miR-142-3p prevents translation of the EEEV genome through binding to complementary miR-142-3p binding sites in the virus 3’ non-translated region (NTR).…”