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miRNA-130a regulates C/EBP-ε expression during granulopoiesis.
- Source :
-
Blood [Blood] 2014 Feb 13; Vol. 123 (7), pp. 1079-89. Date of Electronic Publication: 2014 Jan 07. - Publication Year :
- 2014
-
Abstract
- CCAAT/enhancer binding protein-ε (C/EBP-ε) is considered a master transcription factor regulating terminal neutrophil maturation. It is essential for expression of secondary granule proteins, but it also regulates proliferation, cell cycle, and maturation during granulopoiesis. Cebpe(-/-) mice have incomplete granulocytic differentiation and increased sensitivity toward bacterial infections. The amount of C/EBP-ε messenger RNA (mRNA) increases with maturation from myeloblasts with peak level in myelocytes (MC)/metamyelocytes (MM), when the cells stop proliferating followed by a decline in more mature cells. In contrast, C/EBP-ε protein is virtually detectable only in the MC/MM population, indicating that expression in more immature cells could be inhibited by microRNAs (miRNAs). We found that miRNA-130a (miR-130a) regulates C/EBP-ε protein expression in both murine and human granulocytic precursors. Overexpression of miR-130a in a murine cell line downregulated C/EBP-ε protein and lactoferrin (Ltf), cathelicidin antimicrobial protein (Camp), and lipocalin-2 (Lcn2) mRNA expression giving rise to cells with a more immature phenotype, as seen in the Cebpe(-/-) mouse. Introduction of a C/EBP-ε mRNA without target site for miR-130a restored both C/EBP-ε production, expression of Camp and Lcn2, and resulted in the cells having a more mature phenotype. We conclude that miR-130a is important for the regulation of the timed expression of C/EBP-ε during granulopoiesis.
- Subjects :
- Animals
Cell Differentiation genetics
Cells, Cultured
Gene Expression Regulation
Granulocyte Precursor Cells physiology
HEK293 Cells
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
NIH 3T3 Cells
CCAAT-Enhancer-Binding Proteins genetics
Granulocytes physiology
Leukopoiesis genetics
MicroRNAs physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 123
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 24398327
- Full Text :
- https://doi.org/10.1182/blood-2013-08-523233