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

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dc.contributor.authorStrmiska, Vladislavcs
dc.contributor.authorMichálek, Petrcs
dc.contributor.authorLacková, Zuzanacs
dc.contributor.authorGuráň, Romancs
dc.contributor.authorKřížková, Soňacs
dc.contributor.authorPompeiano Vaníčková, Luciecs
dc.contributor.authorZítka, Ondřejcs
dc.contributor.authorStiborová, Mariecs
dc.contributor.authorEckschlager, Tomášcs
dc.contributor.authorKlejdus, Bořivojcs
dc.contributor.authorPacík, Daliborcs
dc.contributor.authorTvrdíková, Eliškacs
dc.contributor.authorKeil, Claudiacs
dc.contributor.authorHaase, Hajocs
dc.contributor.authorAdam, Vojtěchcs
dc.contributor.authorHeger, Zbyněkcs
dc.coverage.issue5cs
dc.coverage.volume13cs
dc.date.accessioned2020-08-04T11:03:46Z
dc.date.available2020-08-04T11:03:46Z
dc.date.issued2019-05-31cs
dc.description.abstractDNA 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 upregulation 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 in methylated CpG islands in distinct prostate cell lines incubated with sarcosine, but not in cells of nonprostate origin. This phenomenon was further associated with marked upregulation of DNA methyltransferases (Dnmts). Epigenetic changes were recapitulated through blunting of Dnmts using the hypomethylating agent 5-azacytidine, 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 nonmalignant 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.en
dc.formattextcs
dc.format.extent1002-1017cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationMOL ONCOL. 2019, vol. 13, issue 5, p. 1002-1017.en
dc.identifier.doi10.1002/1878-0261.12439cs
dc.identifier.issn1574-7891cs
dc.identifier.other155498cs
dc.identifier.urihttp://hdl.handle.net/11012/180683
dc.language.isoencs
dc.publisherFEBS Presscs
dc.relation.ispartofMOL ONCOLcs
dc.relation.urihttps://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.12439cs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/1574-7891/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectDNA methylationen
dc.subjectDnmtsen
dc.subjectepigeneticsen
dc.subjectprostate canceren
dc.subjectSAMeen
dc.subjectsarcosineen
dc.titleSarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe-Dnmts axisen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-155498en
sync.item.dbtypeVAVen
sync.item.insts2020.08.04 13:03:46en
sync.item.modts2020.08.04 12:30:25en
thesis.grantorVysoké učení technické v Brně. Středoevropský technologický institut VUT. Chytré nanonástrojecs
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