Iron chelation and 2-oxoglutarate-dependent dioxygenase inhibition suppress mantle cell lymphoma's cyclin D1
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F19%3A00521528" target="_blank" >RIV/68378050:_____/19:00521528 - isvavai.cz</a>
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.14655" target="_blank" >https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.14655</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/jcmm.14655" target="_blank" >10.1111/jcmm.14655</a>
Alternative languages
Result language
angličtina
Original language name
Iron chelation and 2-oxoglutarate-dependent dioxygenase inhibition suppress mantle cell lymphoma's cyclin D1
Original language description
The patients with mantle cell lymphoma (MCL) have translocation t(11,14) associated with cyclin D1 overexpression. We observed that iron (an essential cofactor of dioxygenases including prolyl hydroxylases [PHDs]) depletion by deferoxamine blocked MCL cells' proliferation, increased expression of DNA damage marker gamma H2AX, induced cell cycle arrest and decreased cyclin D1 level. Treatment of MCL cell lines with dimethyloxalylglycine, which blocks dioxygenases involving PHDs by competing with their substrate 2-oxoglutarate, leads to their decreased proliferation and the decrease of cyclin D1 level. We then postulated that loss of EGLN2/PHD1 in MCL cells may lead to down-regulation of cyclin D1 by blocking the degradation of FOXO3A, a cyclin D1 suppressor. However, the CRISPR/Cas9-based loss-of-function of EGLN2/PHD1 did not affect cyclin D1 expression and the loss of FOXO3A did not restore cyclin D1 levels after iron chelation. These data suggest that expression of cyclin D1 in MCL is not controlled by ENGL2/PHD1-FOXO3A pathway and that chelation- and 2-oxoglutarate competition-mediated down-regulation of cyclin D1 in MCL cells is driven by yet unknown mechanism involving iron- and 2-oxoglutarate-dependent dioxygenases other than PHD1. These data support further exploration of the use of iron chelation and 2-oxoglutarate-dependent dioxygenase inhibitors as a novel therapy of MCL.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - 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
Result continuities
Project
<a href="/en/project/LO1419" target="_blank" >LO1419: Biomodels for Health - Center for model organisms</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Cellular and Molecular Medicine
ISSN
1582-1838
e-ISSN
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Volume of the periodical
23
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
7785-7795
UT code for WoS article
000488401000001
EID of the result in the Scopus database
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