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
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FD - Oncology and haematology
OECD FORD branch
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Result continuities
Project
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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
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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