Rocha, Sandra M.Sousa, InêsGomes, Inês M.Arinto, PatríciaCosta-Pinheiro, PedroCoutinho, EduardaSantos, Cecília R. A.Jerónimo, CarmenLemos, Manuel C.Passarinha, Luís A.Socorro, SílviaMaia, Cláudio J.2022-07-272022-07-272021-11-172075-1729PURE: 45641918PURE UUID: 379d610c-ed0a-44d2-a0af-3a2308a616bdScopus: 85119680850PubMed: 34833128PubMedCentral: PMC8618799WOS: 000725723500001http://hdl.handle.net/10362/142524No. 007491 No 029114 LA/P/0140/2020 Project Centro-01-0145-FEDER-000019-C4The 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.3067410engBioinformaticsDNA methylationHistone deacetylationProstate cancerSTEAP1Ecology, Evolution, Behavior and SystematicsGeneral Biochemistry,Genetics and Molecular BiologySpace and Planetary SciencePalaeontologySDG 3 - Good Health and Well-beingjournal article10.3390/life11111251https://www.scopus.com/pages/publications/85119680850