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

2021Journal article Open access
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dc.contributor.authorRocha, Sandra
dc.contributor.authorSousa, Inês
dc.contributor.authorGomes, Inês M.
dc.contributor.authorArinto, Patrícia
dc.contributor.authorPinheiro, Pedro Costa
dc.contributor.authorCoutinho, Eduarda
dc.contributor.authorSantos, Cecilia
dc.contributor.authorJerónimo, Carmen
dc.contributor.authorLemos, Manuel C.
dc.contributor.authorPassarinha, L A
dc.contributor.authorSocorro, Sílvia
dc.contributor.authorBaptista, Cláudio Maia
dc.date.accessioned2022-01-20T16:00:32Z
dc.date.available2022-01-20T16:00:32Z
dc.date.issued2021
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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.3390/life11111251pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/11931
dc.language.isoengpt_PT
dc.peerreviewedyespt_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.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectProstate cancerpt_PT
dc.subjectSTEAP1pt_PT
dc.subjectDNA methylationpt_PT
dc.subjectHistone deacetylationpt_PT
dc.subjectBioinformaticspt_PT
dc.titlePromoter Demethylation Upregulates STEAP1 Gene Expression in Human Prostate Cancer: In Vitro and In Silico Analysispt_PT
dc.typejournal article
dspace.entity.typePublication
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.citation.issue11pt_PT
oaire.citation.startPage1251pt_PT
oaire.citation.titleLifept_PT
oaire.citation.volume11pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamOE
person.familyNameRocha
person.familyNameSousa
person.familyNameGomes
person.familyNameArinto
person.familyNameCoutinho
person.familyNameSANTOS
person.familyNameJerónimo
person.familyNameLemos
person.familyNamePaulino Passarinha
person.familyNameSocorro
person.familyNameMaia Baptista
person.givenNameSandra
person.givenNameInês
person.givenNameInês
person.givenNamePatrícia
person.givenNameEduarda
person.givenNameCecília Reis Alves
person.givenNameCarmen
person.givenNameManuel
person.givenNameLuís António
person.givenNameSílvia Cristina da Cruz Marques
person.givenNameCláudio Jorge
person.identifier1918695
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person.identifierhttps://www.researchgate.net/profile/Luis_Passarinha
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project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
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project.funder.nameFundação para a Ciência e a Tecnologia
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rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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