title: 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.
authors.affiliation: Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Lagrange
authors.forename: Romain Z
authors.initials: RZ
authors.lastname: Martin
authors.forename: Nathalie
authors.initials: N
authors.lastname: Droin
authors.forename: Romain
authors.initials: R
authors.lastname: Aucagne
authors.forename: Jérôme
authors.initials: J
authors.lastname: Paggetti
authors.forename: Anne
authors.initials: A
authors.lastname: Largeot
authors.forename: Raphaël
authors.initials: R
authors.lastname: Itzykson
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: Laurent
authors.initials: L
authors.lastname: Delva
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Bastie
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; C497325:EGR1 protein, human; C497326:EGR2 protein, human; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; C491000:NAB2 protein, human; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D012097:Repressor Proteins; D016173:Macrophage Colony-Stimulating Factor