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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F17%3A00487338" target="_blank" >RIV/68378050:_____/17:00487338 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1038/s41467-017-00032-6" target="_blank" >http://dx.doi.org/10.1038/s41467-017-00032-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-017-00032-6" target="_blank" >10.1038/s41467-017-00032-6</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nature Communications

ISSN

2041-1723

e-ISSN

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Volume of the periodical

8

Issue of the periodical within the volume

červen

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

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UT code for WoS article

000404333000005

EID of the result in the Scopus database

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