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Promoter demethylation upregulates STEAP1 gene expression in human prostate cancer

2021-11-17Artigo científico Acesso aberto
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dc.contributor.authorRocha, Sandra M.
dc.contributor.authorSousa, Inês
dc.contributor.authorGomes, Inês M.
dc.contributor.authorArinto, Patrícia
dc.contributor.authorCosta-Pinheiro, Pedro
dc.contributor.authorCoutinho, Eduarda
dc.contributor.authorSantos, Cecília R. A.
dc.contributor.authorJerónimo, Carmen
dc.contributor.authorLemos, Manuel C.
dc.contributor.authorPassarinha, Luís A.
dc.contributor.authorSocorro, Sílvia
dc.contributor.authorMaia, Cláudio J.
dc.contributor.institutionUCIBIO - Applied Molecular Biosciences Unit
dc.contributor.institutionDQ - Departamento de Química
dc.contributor.pblMDPI - Multidisciplinary Digital Publishing Institute
dc.date.accessioned2022-07-27T22:26:24Z
dc.date.available2022-07-27T22:26:24Z
dc.date.issued2021-11-17
dc.descriptionNo. 007491 No 029114 LA/P/0140/2020 Project Centro-01-0145-FEDER-000019-C4
dc.description.abstractThe Six Transmembrane Epithelial Antigen of the Prostate (STEAP1) 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 STEAP1 gene in PCa versus non-neoplastic cells. Bisulfite amplicon sequencing of the CpG island at the STEAP1 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 STEAP1 gene promoter as being demethylated in human PCa, and a negative association with STEAP1 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 STEAP1 mRNA expression. In addition, the involvement of HDAC in the regulation of STEAP1 mRNA expression was corroborated by a negative association between STEAP1 mRNA expression and HDAC4,5,7 and 9 in human PCa. In conclusion, our work indicates that STEAP1 overexpression in PCa can be driven by the hypomethylation of STEAP1 gene promoter.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent3067410
dc.identifier.doi10.3390/life11111251
dc.identifier.issn2075-1729
dc.identifier.otherPURE: 45641918
dc.identifier.otherPURE UUID: 379d610c-ed0a-44d2-a0af-3a2308a616bd
dc.identifier.otherScopus: 85119680850
dc.identifier.otherPubMed: 34833128
dc.identifier.otherPubMedCentral: PMC8618799
dc.identifier.otherWOS: 000725723500001
dc.identifier.urihttp://hdl.handle.net/10362/142524
dc.identifier.urlhttps://www.scopus.com/pages/publications/85119680850
dc.language.isoeng
dc.peerreviewedyes
dc.relationinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00709%2F2020/PT
dc.relationHealth Sciences Research Centre
dc.relationApplied Molecular Biosciences Unit
dc.relationApplied Molecular Biosciences Unit
dc.relationUnrevealing the effect of STEAP1 knockdown in prostate cancer cells: from protein expression profile to clinical applications
dc.relationStructural and Functional Characterization of Cancer-associated Epithelial Antigen STEAP1
dc.relationinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBSAB%2F150376%2F2019/PT
dc.subjectBioinformatics
dc.subjectDNA methylation
dc.subjectHistone deacetylation
dc.subjectProstate cancer
dc.subjectSTEAP1
dc.subjectEcology, Evolution, Behavior and Systematics
dc.subjectGeneral Biochemistry,Genetics and Molecular Biology
dc.subjectSpace and Planetary Science
dc.subjectPalaeontology
dc.subjectSDG 3 - Good Health and Well-being
dc.titlePromoter demethylation upregulates STEAP1 gene expression in human prostate canceren
dc.title.subtitleAnd in silico analysisen
dc.typejournal article
degois.publication.issue11
degois.publication.titleLife
degois.publication.volume11
dspace.entity.typePublication
oaire.awardNumberUIDB/00709/2020
oaire.awardNumberUIDB/04378/2020
oaire.awardNumberUIDP/04378/2020
oaire.awardNumberSFRH/BD/115693/2016
oaire.awardNumberSFRH/BSAB/150376/2019
oaire.awardTitleHealth Sciences Research Centre
oaire.awardTitleApplied Molecular Biosciences Unit
oaire.awardTitleApplied Molecular Biosciences Unit
oaire.awardTitleUnrevealing the effect of STEAP1 knockdown in prostate cancer cells: from protein expression profile to clinical applications
oaire.awardTitleStructural and Functional Characterization of Cancer-associated Epithelial Antigen STEAP1
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00709%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F115693%2F2016/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBSAB%2F150376%2F2019/PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamOE
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
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