| First Author | Larsen MT | Year | 2014 |
| Journal | Blood | Volume | 123 |
| Issue | 7 | Pages | 1079-89 |
| PubMed ID | 24398327 | Mgi Jnum | J:208687 |
| Mgi Id | MGI:5564831 | Doi | 10.1182/blood-2013-08-523233 |
| Citation | Larsen MT, et al. (2014) miRNA-130a regulates C/EBP-epsilon expression during granulopoiesis. Blood 123(7):1079-89 |
| abstractText | CCAAT/enhancer binding protein-epsilon (C/EBP-epsilon) 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-epsilon 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-epsilon 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-epsilon protein expression in both murine and human granulocytic precursors. Overexpression of miR-130a in a murine cell line downregulated C/EBP-epsilon 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-epsilon mRNA without target site for miR-130a restored both C/EBP-epsilon 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-epsilon during granulopoiesis. |
