ENPP2 Methylation in Health and Cancer

Autotaxin (ATX) encoded by Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (ENPP2) is a key enzyme in Lysophosphatidic Acid (LPA) synthesis implicated in cancer. Although its aberrant expression has been reported, ENPP2 methylation profiles in health and mali...

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Autores principales:	Maria Panagopoulou, Dionysios Fanidis, Vassilis Aidinis, Ekaterini Chatzaki
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	autotaxin <i>ENPP2</i> methylation cancer expression regulation Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/29ac7e1b669643908fbcbf1f61ad86cf
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id	oai:doaj.org-article:29ac7e1b669643908fbcbf1f61ad86cf
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spelling	oai:doaj.org-article:29ac7e1b669643908fbcbf1f61ad86cf2021-11-11T17:23:00Z<i>ENPP2</i> Methylation in Health and Cancer10.3390/ijms2221119581422-00671661-6596https://doaj.org/article/29ac7e1b669643908fbcbf1f61ad86cf2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11958https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Autotaxin (ATX) encoded by Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (<i>ENPP2</i>) is a key enzyme in Lysophosphatidic Acid (LPA) synthesis implicated in cancer. Although its aberrant expression has been reported, <i>ENPP2</i> methylation profiles in health and malignancy are not described. We examined in silico the methylation of <i>ENPP2</i> analyzing publicly available methylome datasets, to identify Differentially Methylated CpGs (DMCs) which were then correlated with expression at gene and isoform levels. Significance indication was set to be FDR corrected <i>p</i>-value < 0.05. Healthy tissues presented methylation in all gene body CGs and lower levels in Promoter Associated (PA) regions, whereas in the majority of the tumors examined (HCC, melanoma, CRC, LC and PC) the methylation pattern was reversed. DMCs identified in the promoter were located in sites recognized by multiple transcription factors, suggesting involvement in gene expression. Alterations in methylation were correlated to an aggressive phenotype in cancer cell lines. In prostate and lung adenocarcinomas, increased methylation of PA CGs was correlated to decreased <i>ENPP2</i> mRNA expression and to poor prognosis parameters. Collectively, our results corroborate that methylation is an active level of ATX expression regulation in cancer. Our study provides an extended description of the methylation status of <i>ENPP2</i> in health and cancer and points out specific DMCs of value as prognostic biomarkers.Maria PanagopoulouDionysios FanidisVassilis AidinisEkaterini ChatzakiMDPI AGarticleautotaxin<i>ENPP2</i>methylationcancerexpressionregulationBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11958, p 11958 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autotaxin <i>ENPP2</i> methylation cancer expression regulation Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	autotaxin <i>ENPP2</i> methylation cancer expression regulation Biology (General) QH301-705.5 Chemistry QD1-999 Maria Panagopoulou Dionysios Fanidis Vassilis Aidinis Ekaterini Chatzaki <i>ENPP2</i> Methylation in Health and Cancer
description	Autotaxin (ATX) encoded by Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (<i>ENPP2</i>) is a key enzyme in Lysophosphatidic Acid (LPA) synthesis implicated in cancer. Although its aberrant expression has been reported, <i>ENPP2</i> methylation profiles in health and malignancy are not described. We examined in silico the methylation of <i>ENPP2</i> analyzing publicly available methylome datasets, to identify Differentially Methylated CpGs (DMCs) which were then correlated with expression at gene and isoform levels. Significance indication was set to be FDR corrected <i>p</i>-value < 0.05. Healthy tissues presented methylation in all gene body CGs and lower levels in Promoter Associated (PA) regions, whereas in the majority of the tumors examined (HCC, melanoma, CRC, LC and PC) the methylation pattern was reversed. DMCs identified in the promoter were located in sites recognized by multiple transcription factors, suggesting involvement in gene expression. Alterations in methylation were correlated to an aggressive phenotype in cancer cell lines. In prostate and lung adenocarcinomas, increased methylation of PA CGs was correlated to decreased <i>ENPP2</i> mRNA expression and to poor prognosis parameters. Collectively, our results corroborate that methylation is an active level of ATX expression regulation in cancer. Our study provides an extended description of the methylation status of <i>ENPP2</i> in health and cancer and points out specific DMCs of value as prognostic biomarkers.
format	article
author	Maria Panagopoulou Dionysios Fanidis Vassilis Aidinis Ekaterini Chatzaki
author_facet	Maria Panagopoulou Dionysios Fanidis Vassilis Aidinis Ekaterini Chatzaki
author_sort	Maria Panagopoulou
title	<i>ENPP2</i> Methylation in Health and Cancer
title_short	<i>ENPP2</i> Methylation in Health and Cancer
title_full	<i>ENPP2</i> Methylation in Health and Cancer
title_fullStr	<i>ENPP2</i> Methylation in Health and Cancer
title_full_unstemmed	<i>ENPP2</i> Methylation in Health and Cancer
title_sort	<i>enpp2</i> methylation in health and cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/29ac7e1b669643908fbcbf1f61ad86cf
work_keys_str_mv	AT mariapanagopoulou ienpp2imethylationinhealthandcancer AT dionysiosfanidis ienpp2imethylationinhealthandcancer AT vassilisaidinis ienpp2imethylationinhealthandcancer AT ekaterinichatzaki ienpp2imethylationinhealthandcancer
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<i>ENPP2</i> Methylation in Health and Cancer

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