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: | , , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/0402a91b6d81454fbdeaebe334eda5df |
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| Sumario: | 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. |
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