Epigenetic regulation of the STEAP1 gene in prostate cancer samples

Authors and affiliations:

Sandra M Rocha ¹, Inês Sousa ^1,2, Inês M Gomes ¹, Patrícia Arinto ¹, Pedro Costa-Pinheiro ³, Eduarda Coutinho ¹, Cecília R Santos ¹, Carmen Jerónimo ^3,4, Manuel C Lemos ^1,5, Luís A Passarinha ^1,6,7,8, Sílvia Socorro ¹, Cláudio J Maia ^1,5

¹ CICS-UBI-Health Sciences Research Center, Universidade da Beira Interior, 6201-506 Covilhã, Portugal.

² Department of Medical Sciences, Institute of Biomedicine-iBiMED, Universidade de Aveiro, 3810-193 Aveiro, Portugal.

³ Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal.

⁴ Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences, Universidade do Porto (ICBAS-UP), 4050-513 Porto, Portugal.

⁵ C4-UBI, Cloud Computing Competence Center, Universidade da Beira Interior, 6200-501 Covilhã, Portugal.

⁶ Associate Laboratory i4HB-Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2819-516 Caparica, Portugal.

⁷ UCIBIO-Applied Molecular Biosciences Unit, Department of Chemistry, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2819-516 Caparica, Portugal.

⁸ Laboratório de Fármaco-Toxicologia-UBIMedical, Universidade da Beira Interior, 6201-284 Covilhã, Portugal.

Abstract:

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.

Journal: Life (Basel)

Link: https://www.mdpi.com/2075-1729/11/11/1251