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

Biochim Biophys Acta. 2013 Aug;1833(8):1936-46. doi: 10.1016/j.bbamcr.2013.04.007. Epub 2013 Apr 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism
  • Early Growth Response Protein 2 / genetics
  • Early Growth Response Protein 2 / metabolism
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Humans
  • K562 Cells
  • Leukemia, Myelomonocytic, Chronic / genetics
  • Leukemia, Myelomonocytic, Chronic / metabolism
  • Leukemia, Myelomonocytic, Chronic / pathology
  • Macrophage Colony-Stimulating Factor / pharmacology*
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Macrophages / physiology*
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Monocytes / cytology
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Monocytes / physiology*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Up-Regulation / drug effects

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • EGR1 protein, human
  • EGR2 protein, human
  • Early Growth Response Protein 1
  • Early Growth Response Protein 2
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • MIRN142 microRNA, human
  • MicroRNAs
  • NAB2 protein, human
  • Receptors, Cell Surface
  • Receptors, IgG
  • Repressor Proteins
  • Macrophage Colony-Stimulating Factor