Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe-Dnmts axis

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11310/19:10394589 RIV/00216224:14110/19:00112354 RIV/00216208:11130/19:10394589 RIV/00216305:26620/19:PU131089 a 2 dalších

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe-Dnmts axis

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe-Dnmts axis

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Molecular Oncology

ISSN

1574-7891

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

1002-1017

Kód UT WoS článku

000477090700002

EID výsledku v databázi Scopus

2-s2.0-85065048465