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miR-139-5p controls translation in myeloid leukemia through EIF4G2

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F16%3A10323619" target="_blank" >RIV/00064203:_____/16:10323619 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11130/16:10323619

  • Result on the web

    <a href="http://dx.doi.org/10.1038/onc.2015.247" target="_blank" >http://dx.doi.org/10.1038/onc.2015.247</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1038/onc.2015.247" target="_blank" >10.1038/onc.2015.247</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    miR-139-5p controls translation in myeloid leukemia through EIF4G2

  • Original language description

    MicroRNAs (miRNAs) are crucial components of homeostatic and developmental gene regulation. In turn, dysregulation of miRNA expression is a common feature of different types of cancer, which can be harnessed therapeutically. Here we identify miR-139-5p suppression across several cytogenetically defined acute myeloid leukemia (AML) subgroups. The promoter of mir-139 was transcriptionally silenced and could be reactivated by histone deacetylase inhibitors in a dose-dependent manner. Restoration of mir-139 expression in cell lines representing the major AML subgroups (t[8;21], inv[16], mixed lineage leukemia-rearranged and complex karyotype AML) caused cell cycle arrest and apoptosis in vitro and in xenograft mouse models in vivo. During normal hematopoiesis, mir-139 is exclusively expressed in terminally differentiated neutrophils and macrophages. Ectopic expression of mir-139 repressed proliferation of normal CD34(+)-hematopoietic stem and progenitor cells and perturbed myelomonocytic in vitro differentiation. Mechanistically, mir-139 exerts its effects by repressing the translation initiation factor EIF4G2, thereby reducing overall protein synthesis while specifically inducing the translation of cell cycle inhibitor p27(Kip1). Knockdown of EIF4G2 recapitulated the effects of mir-139, whereas restoring EIF4G2 expression rescued the mir-139 phenotype. Moreover, elevated miR-139-5p expression is associated with a favorable outcome in a cohort of 165 pediatric patients with AML. Thus, mir-139 acts as a global tumor suppressor-miR in AML by controlling protein translation. As AML cells are dependent on high protein synthesis rates controlling the expression of mir-139 constitutes a novel path for the treatment of AML.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    FD - Oncology and haematology

  • OECD FORD branch

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2016

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    Oncogene

  • ISSN

    0950-9232

  • e-ISSN

  • Volume of the periodical

    35

  • Issue of the periodical within the volume

    14

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    10

  • Pages from-to

    1822-1831

  • UT code for WoS article

    000373610400008

  • EID of the result in the Scopus database

    2-s2.0-84957921951