| First Author | Wurm AA | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 46 |
| PubMed ID | 28663557 | Mgi Jnum | J:249065 |
| Mgi Id | MGI:5921585 | Doi | 10.1038/s41467-017-00032-6 |
| Citation | Wurm AA, et al. (2017) Disruption of the C/EBPalpha-miR-182 balance impairs granulocytic differentiation. Nat Commun 8(1):46 |
| abstractText | Transcription factor C/EBPalpha is a master regulator of myelopoiesis and its inactivation is associated with acute myeloid leukemia. Deregulation of C/EBPalpha by microRNAs during granulopoiesis or acute myeloid leukemia development has not been studied. Here we show that oncogenic miR-182 is a strong regulator of C/EBPalpha. Moreover, we identify a regulatory loop between C/EBPalpha and miR-182. While C/EBPalpha blocks miR-182 expression by direct promoter binding during myeloid differentiation, enforced expression of miR-182 reduces C/EBPalpha protein level and impairs granulopoiesis in vitro and in vivo. In addition, miR-182 expression is highly elevated particularly in acute myeloid leukemia patients with C-terminal CEBPA mutations, thereby depicting a mechanism by which C/EBPalpha blocks miR-182 expression. Furthermore, we present miR-182 expression as a prognostic marker in cytogenetically high-risk acute myeloid leukemia patients. Our data demonstrate the importance of a controlled balance between C/EBPalpha and miR-182 for the maintenance of healthy granulopoiesis.C/EBPalpha is a critical transcription factor involved in myelopoiesis and its inactivation is associated with acute myeloid leukemia (AML). Here the authors show a negative feedback loop between C/EBPalpha and miR-182 and identify this miRNA as a marker of high-risk AML. |
