Počet záznamů: 1  

Disruption of the C/EBP alpha-miR-182 balance impairs granulocytic differentiation

  1. 1.
    0487338 - UMG-J 2018 RIV GB eng J - Článek v odborném periodiku
    Wurm, A.A. - Zjablovskaja, Polina - Kardošová, Miroslava - Gerloff, D. - Braeuer-Hartmann, D. - Katzerke, C. - Hartmann, J.U. - Benoukraf, T. - Fricke, S. - Hilger, N. - Mueller, A.M. - Bill, M. - Schwind, S. - Tenen, D.G. - Niederwieser, D. - Alberich-Jorda, Meritxell - Behre, G.
    Disruption of the C/EBP alpha-miR-182 balance impairs granulocytic differentiation.
    Nature Communications. Roč. 8, červen (2017), č. článku 46. ISSN 2041-1723
    Institucionální podpora: RVO:68378050
    Klíčová slova: acute myeloid-leukemia * colony-stimulating factor * acute promyelocytic leukemia * hematopoietic stem-cells * c/ebp-alpha function * gene-expression * cebpa mutations * cycle control * up-regulation * in-vivo
    Kód oboru RIV: EB - Genetika a molekulární biologie
    Obor OECD: Cell biology
    Impakt faktor: 12.353, rok: 2017

    Transcription factor C/EBP alpha is a master regulator of myelopoiesis and its inactivation is associated with acute myeloid leukemia. Deregulation of C/EBP alpha 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 alpha. Moreover, we identify a regulatory loop between C/EBP alpha and miR-182. While C/EBP alpha blocks miR-182 expression by direct promoter binding during myeloid differentiation, enforced expression of miR-182 reduces C/EBP alpha 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 alpha 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 alpha and miR-182 for the maintenance of healthy granulopoiesis.
    Trvalý link: http://hdl.handle.net/11104/0281986