Promoter Demethylation Upregulates <i>STEAP1</i> Gene Expression in Human Prostate Cancer: In Vitro and In Silico Analysis

The Six Transmembrane Epithelial Antigen of the Prostate (<i>STEAP1</i>) is an oncogene overexpressed in several human tumors, particularly in prostate cancer (PCa). However, the mechanisms involved in its overexpression remain unknown. It is well known that epigenetic modifications may...

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Autores principales:	Sandra M. Rocha, Inês Sousa, Inês M. Gomes, Patrícia Arinto, Pedro Costa-Pinheiro, Eduarda Coutinho, Cecília R. Santos, Carmen Jerónimo, Manuel C. Lemos, Luís A. Passarinha, Sílvia Socorro, Cláudio J. Maia
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	prostate cancer <i>STEAP1</i> DNA methylation histone deacetylation bioinformatics Science Q
Acceso en línea:	https://doaj.org/article/0402a91b6d81454fbdeaebe334eda5df
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spelling	oai:doaj.org-article:0402a91b6d81454fbdeaebe334eda5df2021-11-25T18:11:35ZPromoter Demethylation Upregulates <i>STEAP1</i> Gene Expression in Human Prostate Cancer: In Vitro and In Silico Analysis10.3390/life111112512075-1729https://doaj.org/article/0402a91b6d81454fbdeaebe334eda5df2021-11-01T00:00:00Zhttps://www.mdpi.com/2075-1729/11/11/1251https://doaj.org/toc/2075-1729The Six Transmembrane Epithelial Antigen of the Prostate (<i>STEAP1</i>) is an oncogene overexpressed in several human tumors, particularly in prostate cancer (PCa). However, the mechanisms involved in its overexpression remain unknown. It is well known that epigenetic modifications may result in abnormal gene expression patterns, contributing to tumor initiation and progression. Therefore, this study aimed to analyze the methylation pattern of the <i>STEAP1</i> gene in PCa versus non-neoplastic cells. Bisulfite amplicon sequencing of the CpG island at the <i>STEAP1</i> gene promoter showed a higher methylation level in non-neoplastic PNT1A prostate cells than in human PCa samples. Bioinformatic analysis of the GEO datasets also showed the <i>STEAP1</i> gene promoter as being demethylated in human PCa, and a negative association with <i>STEAP1</i> mRNA expression was observed. These results are supported by the treatment of non-neoplastic PNT1A cells with DNMT and HDAC inhibitors, which induced a significant increase in <i>STEAP1</i> mRNA expression. In addition, the involvement of HDAC in the regulation of <i>STEAP1</i> mRNA expression was corroborated by a negative association between <i>STEAP1</i> mRNA expression and <i>HDAC4,5,7</i> and <i>9</i> in human PCa. In conclusion, our work indicates that <i>STEAP1</i> overexpression in PCa can be driven by the hypomethylation of <i>STEAP1</i> gene promoter.Sandra M. RochaInês SousaInês M. GomesPatrícia ArintoPedro Costa-PinheiroEduarda CoutinhoCecília R. SantosCarmen JerónimoManuel C. LemosLuís A. PassarinhaSílvia SocorroCláudio J. MaiaMDPI AGarticleprostate cancer<i>STEAP1</i>DNA methylationhistone deacetylationbioinformaticsScienceQENLife, Vol 11, Iss 1251, p 1251 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	prostate cancer <i>STEAP1</i> DNA methylation histone deacetylation bioinformatics Science Q
spellingShingle	prostate cancer <i>STEAP1</i> DNA methylation histone deacetylation bioinformatics Science Q Sandra M. Rocha Inês Sousa Inês M. Gomes Patrícia Arinto Pedro Costa-Pinheiro Eduarda Coutinho Cecília R. Santos Carmen Jerónimo Manuel C. Lemos Luís A. Passarinha Sílvia Socorro Cláudio J. Maia Promoter Demethylation Upregulates <i>STEAP1</i> Gene Expression in Human Prostate Cancer: In Vitro and In Silico Analysis
description	The Six Transmembrane Epithelial Antigen of the Prostate (<i>STEAP1</i>) is an oncogene overexpressed in several human tumors, particularly in prostate cancer (PCa). However, the mechanisms involved in its overexpression remain unknown. It is well known that epigenetic modifications may result in abnormal gene expression patterns, contributing to tumor initiation and progression. Therefore, this study aimed to analyze the methylation pattern of the <i>STEAP1</i> gene in PCa versus non-neoplastic cells. Bisulfite amplicon sequencing of the CpG island at the <i>STEAP1</i> gene promoter showed a higher methylation level in non-neoplastic PNT1A prostate cells than in human PCa samples. Bioinformatic analysis of the GEO datasets also showed the <i>STEAP1</i> gene promoter as being demethylated in human PCa, and a negative association with <i>STEAP1</i> mRNA expression was observed. These results are supported by the treatment of non-neoplastic PNT1A cells with DNMT and HDAC inhibitors, which induced a significant increase in <i>STEAP1</i> mRNA expression. In addition, the involvement of HDAC in the regulation of <i>STEAP1</i> mRNA expression was corroborated by a negative association between <i>STEAP1</i> mRNA expression and <i>HDAC4,5,7</i> and <i>9</i> in human PCa. In conclusion, our work indicates that <i>STEAP1</i> overexpression in PCa can be driven by the hypomethylation of <i>STEAP1</i> gene promoter.
format	article
author	Sandra M. Rocha Inês Sousa Inês M. Gomes Patrícia Arinto Pedro Costa-Pinheiro Eduarda Coutinho Cecília R. Santos Carmen Jerónimo Manuel C. Lemos Luís A. Passarinha Sílvia Socorro Cláudio J. Maia
author_facet	Sandra M. Rocha Inês Sousa Inês M. Gomes Patrícia Arinto Pedro Costa-Pinheiro Eduarda Coutinho Cecília R. Santos Carmen Jerónimo Manuel C. Lemos Luís A. Passarinha Sílvia Socorro Cláudio J. Maia
author_sort	Sandra M. Rocha
title	Promoter Demethylation Upregulates <i>STEAP1</i> Gene Expression in Human Prostate Cancer: In Vitro and In Silico Analysis
title_short	Promoter Demethylation Upregulates <i>STEAP1</i> Gene Expression in Human Prostate Cancer: In Vitro and In Silico Analysis
title_full	Promoter Demethylation Upregulates <i>STEAP1</i> Gene Expression in Human Prostate Cancer: In Vitro and In Silico Analysis
title_fullStr	Promoter Demethylation Upregulates <i>STEAP1</i> Gene Expression in Human Prostate Cancer: In Vitro and In Silico Analysis
title_full_unstemmed	Promoter Demethylation Upregulates <i>STEAP1</i> Gene Expression in Human Prostate Cancer: In Vitro and In Silico Analysis
title_sort	promoter demethylation upregulates <i>steap1</i> gene expression in human prostate cancer: in vitro and in silico analysis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0402a91b6d81454fbdeaebe334eda5df
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Promoter Demethylation Upregulates <i>STEAP1</i> Gene Expression in Human Prostate Cancer: In Vitro and In Silico Analysis

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