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

 
: Wurm, Alexander Arthur; Zjablovskaja, Polina; Kardosova, Miroslava; Gerloff, Dennis; Bräuer-Hartmann, Daniela; Katzerke, Christiane; Hartmann, Jens Uwe; Benoukraf, Touati; Fricke, Stephan; Hilger, Nadja; Müller, Anne Marie; Bill, Marius; Schwind, Sebastian; Tenen, Daniel G.; Niederwieser, Dietger Walter; Jordà, Meritxell Alberich; Behre, Gerhard F.

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Volltext (PDF; )

Nature Communications 8 (2017), Art. 46, 16 S.
ISSN: 2041-1723
Englisch
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer IZI ()

Abstract
Transcription factor C/EBPα is a master regulator of myelopoiesis and its inactivation is associated with acute myeloid leukemia. Deregulation of C/EBPα 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/EBPα. Moreover, we identify a regulatory loop between C/EBPα and miR-182. While C/EBPα blocks miR-182 expression by direct promoter binding during myeloid differentiation, enforced expression of miR-182 reduces C/EBPα 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/EBPα 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/EBPα and miR-182 for the maintenance of healthy granulopoiesis.

: http://publica.fraunhofer.de/dokumente/N-470540.html