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https://doi.org/10.1038/s41467-017-00032-6
| Title: | Disruption of the C/EBP? - MiR-182 balance impairs granulocytic differentiation | Authors: | Wurm, A.A Zjablovskaja, P Kardosova, M Gerloff, D Bräuer-Hartmann, D Katzerke, C Hartmann, J.-U Benoukraf, T Fricke, S Hilger, N Müller, A.-M Bill, M Schwind, S Tenen, D.G Niederwieser, D Alberich-Jorda, M Behre, G |
Keywords: | CCAAT enhancer binding protein alpha microRNA 182 CCAAT enhancer binding protein CEBPA protein, human CEBPA protein, mouse microRNA Mirn182 microRNA, human Mirn182 microRNA, mouse biological development cancer chemical binding gene expression genetic analysis genetic marker laboratory method mutation protein acute myeloid leukemia animal cell animal experiment animal model animal tissue Article bone marrow cell carboxy terminal sequence cell differentiation controlled study downstream processing gene disruption gene mutation gene targeting granulocyte granulopoiesis human human cell in vitro study in vivo study mouse nonhuman oncogene promoter region animal cell differentiation genetics knockout mouse leukopoiesis metabolism mortality prognosis real time polymerase chain reaction Western blotting Animals Blotting, Western CCAAT-Enhancer-Binding Proteins Cell Differentiation Granulocytes Humans Leukemia, Myeloid, Acute Leukopoiesis Mice Mice, Knockout MicroRNAs Prognosis Real-Time Polymerase Chain Reaction |
Issue Date: | 2017 | Publisher: | Nature Publishing Group | Citation: | Wurm, A.A, Zjablovskaja, P, Kardosova, M, Gerloff, D, Bräuer-Hartmann, D, Katzerke, C, Hartmann, J.-U, Benoukraf, T, Fricke, S, Hilger, N, Müller, A.-M, Bill, M, Schwind, S, Tenen, D.G, Niederwieser, D, Alberich-Jorda, M, Behre, G (2017). Disruption of the C/EBP? - MiR-182 balance impairs granulocytic differentiation. Nature Communications 8 (1) : 32. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-017-00032-6 | Rights: | Attribution 4.0 International | Abstract: | Transcription factor C/EBP? is a master regulator of myelopoiesis and its inactivation is associated with acute myeloid leukemia. Deregulation of C/EBP? 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/EBP?. Moreover, we identify a regulatory loop between C/EBP? and miR-182. While C/EBP? blocks miR-182 expression by direct promoter binding during myeloid differentiation, enforced expression of miR-182 reduces C/EBP? 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/EBP? 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/EBP? and miR-182 for the maintenance of healthy granulopoiesis. © 2017 The Author(s). | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/178606 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-017-00032-6 | Rights: | Attribution 4.0 International |
| Appears in Collections: | Staff Publications Elements |
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