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

Author

Listed:
  • Alexander Arthur Wurm

    (Leipzig University Hospital)

  • Polina Zjablovskaja

    (Academy of Sciences of the Czech Republic)

  • Miroslava Kardosova

    (Academy of Sciences of the Czech Republic)

  • Dennis Gerloff

    (Leipzig University Hospital)

  • Daniela Bräuer-Hartmann

    (Leipzig University Hospital)

  • Christiane Katzerke

    (Leipzig University Hospital)

  • Jens-Uwe Hartmann

    (Leipzig University Hospital)

  • Touati Benoukraf

    (National University of Singapore)

  • Stephan Fricke

    (Fraunhofer Institute for Cell Therapy and Immunology)

  • Nadja Hilger

    (Fraunhofer Institute for Cell Therapy and Immunology)

  • Anne-Marie Müller

    (Fraunhofer Institute for Cell Therapy and Immunology)

  • Marius Bill

    (Leipzig University Hospital)

  • Sebastian Schwind

    (Leipzig University Hospital)

  • Daniel G. Tenen

    (National University of Singapore
    Harvard Stem Cell Institute, Harvard Medical School)

  • Dietger Niederwieser

    (Leipzig University Hospital)

  • Meritxell Alberich-Jorda

    (Academy of Sciences of the Czech Republic)

  • Gerhard Behre

    (Leipzig University Hospital)

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.

Suggested Citation

  • Alexander Arthur Wurm & Polina Zjablovskaja & Miroslava Kardosova & Dennis Gerloff & Daniela Bräuer-Hartmann & Christiane Katzerke & Jens-Uwe Hartmann & Touati Benoukraf & Stephan Fricke & Nadja Hilge, 2017. "Disruption of the C/EBPα—miR-182 balance impairs granulocytic differentiation," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00032-6
    DOI: 10.1038/s41467-017-00032-6
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    Cited by:

    1. Dongmei Wang & Tao Sun & Yuan Xia & Zhe Zhao & Xue Sheng & Shuying Li & Yuechan Ma & Mingying Li & Xiuhua Su & Fan Zhang & Peng Li & Daoxin Ma & Jingjing Ye & Fei Lu & Chunyan Ji, 2023. "Homodimer-mediated phosphorylation of C/EBPα-p42 S16 modulates acute myeloid leukaemia differentiation through liquid-liquid phase separation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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