Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe-Dnmts axis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62156489%3A43210%2F19%3A43914793" target="_blank" >RIV/62156489:43210/19:43914793 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/19:10394589 RIV/00216224:14110/19:00112354 RIV/00216208:11130/19:10394589 RIV/00216305:26620/19:PU131089 and 2 more
Result on the web
<a href="https://doi.org/10.1002/1878-0261.12439" target="_blank" >https://doi.org/10.1002/1878-0261.12439</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/1878-0261.12439" target="_blank" >10.1002/1878-0261.12439</a>
Alternative languages
Result language
angličtina
Original language name
Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe-Dnmts axis
Original language description
DNA hypermethylation is one of the most common epigenetic modifications in prostate cancer (PCa). Several studies have delineated sarcosine as a PCa oncometabolite that increases the migration of malignant prostate cells while decreasing their doubling time. Here, we show that incubation of prostate cells with sarcosine elicited the up-regulation of sarcosine N-demethylation enzymes, sarcosine dehydrogenase, and pipecolic acid oxidase. This process was accompanied by a considerable increase in the production of the major methyl-donor S-adenosylmethionine (SAMe), together with an elevation of cellular methylation potential. Global DNA methylation analyses revealed increases of methylated CpG islands in distinct prostate cell lines incubated with sarcosine, but not in cells of non-prostate origin. This phenomenon was further associated with marked up-regulation of DNA methyltransferases (Dnmts). Epigenetic changes were recapitulated through blunting of Dnmts using the hypomethylating agent 5-azacytidine (5-Aza), which was able to inhibit sarcosine-induced migration of prostate cells. Moreover, spatial mapping revealed concomitant increases in sarcosine, SAMe, and Dnmt1 in histologically-confirmed malignant prostate tissue, but not in adjacent or non-malignant tissue, which is in line with the obtained in vitro data. In summary, we show here for the first time that sarcosine acts as an epigenetic modifier of prostate cells, and that this may contribute to its oncometabolic role.
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
30204 - Oncology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
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
Molecular Oncology
ISSN
1574-7891
e-ISSN
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Volume of the periodical
13
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
1002-1017
UT code for WoS article
000477090700002
EID of the result in the Scopus database
2-s2.0-85065048465