Name: | Description: | Size: | Format: | |
---|---|---|---|---|
2.93 MB | Adobe PDF |
Advisor(s)
Abstract(s)
The 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.
Description
Keywords
Prostate cancer STEAP1 DNA methylation Histone deacetylation Bioinformatics