Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe‐Dnmts axis
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...
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doaj-04f0e5a202ed485ea5b906c03279d7892020-11-25T03:57:33ZengWileyMolecular Oncology1574-78911878-02612019-05-011351002101710.1002/1878-0261.12439Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe‐Dnmts axisVladislav Strmiska0Petr Michalek1Zuzana Lackova2Roman Guran3Sona Krizkova4Lucie Vanickova5Ondrej Zitka6Marie Stiborova7Tomas Eckschlager8Borivoj Klejdus9Dalibor Pacik10Eliska Tvrdikova11Claudia Keil12Hajo Haase13Vojtech Adam14Zbynek Heger15Department of Chemistry and Biochemistry Mendel University in Brno Czech RepublicDepartment of Chemistry and Biochemistry Mendel University in Brno Czech RepublicDepartment of Chemistry and Biochemistry Mendel University in Brno Czech RepublicDepartment of Chemistry and Biochemistry Mendel University in Brno Czech RepublicDepartment of Chemistry and Biochemistry Mendel University in Brno Czech RepublicDepartment of Chemistry and Biochemistry Mendel University in Brno Czech RepublicDepartment of Chemistry and Biochemistry Mendel University in Brno Czech RepublicDepartment of Biochemistry Faculty of Science Charles University Prague 2 Czech RepublicDepartment of Paediatric Haematology and Oncology 2nd Faculty of Medicine Charles University University Hospital Motol Prague 5 Czech RepublicDepartment of Chemistry and Biochemistry Mendel University in Brno Czech RepublicDepartment of Urology University Hospital Brno Brno Czech RepublicDepartment of Pathology University Hospital Brno Czech RepublicDepartment of Food Chemistry and Toxicology Technical University of Berlin GermanyDepartment of Food Chemistry and Toxicology Technical University of Berlin GermanyDepartment of Chemistry and Biochemistry Mendel University in Brno Czech RepublicDepartment of Chemistry and Biochemistry Mendel University in Brno Czech RepublicDNA 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.https://doi.org/10.1002/1878-0261.12439DNA methylationDnmtsepigeneticsprostate cancerSAMesarcosine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Vladislav Strmiska Petr Michalek Zuzana Lackova Roman Guran Sona Krizkova Lucie Vanickova Ondrej Zitka Marie Stiborova Tomas Eckschlager Borivoj Klejdus Dalibor Pacik Eliska Tvrdikova Claudia Keil Hajo Haase Vojtech Adam Zbynek Heger |
spellingShingle |
Vladislav Strmiska Petr Michalek Zuzana Lackova Roman Guran Sona Krizkova Lucie Vanickova Ondrej Zitka Marie Stiborova Tomas Eckschlager Borivoj Klejdus Dalibor Pacik Eliska Tvrdikova Claudia Keil Hajo Haase Vojtech Adam Zbynek Heger Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe‐Dnmts axis Molecular Oncology DNA methylation Dnmts epigenetics prostate cancer SAMe sarcosine |
author_facet |
Vladislav Strmiska Petr Michalek Zuzana Lackova Roman Guran Sona Krizkova Lucie Vanickova Ondrej Zitka Marie Stiborova Tomas Eckschlager Borivoj Klejdus Dalibor Pacik Eliska Tvrdikova Claudia Keil Hajo Haase Vojtech Adam Zbynek Heger |
author_sort |
Vladislav Strmiska |
title |
Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe‐Dnmts axis |
title_short |
Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe‐Dnmts axis |
title_full |
Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe‐Dnmts axis |
title_fullStr |
Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe‐Dnmts axis |
title_full_unstemmed |
Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe‐Dnmts axis |
title_sort |
sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the same‐dnmts axis |
publisher |
Wiley |
series |
Molecular Oncology |
issn |
1574-7891 1878-0261 |
publishDate |
2019-05-01 |
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 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. |
topic |
DNA methylation Dnmts epigenetics prostate cancer SAMe sarcosine |
url |
https://doi.org/10.1002/1878-0261.12439 |
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