Effect of aberrantly methylated androgen receptor target gene PCDH7 on the development of androgen-independent prostate cancer cells.

Abstract

Androgen-independent prostate cancer (AIPC) is an extremely malignant tumor developed from the androgen dependent (ADPC). However, the mechanism of transition process from ADPC to AIPC remains unknown. Here we aimed to identify the androgen receptor (AR) target gene and its roles in AIPC. Target genes of AR were identified by ChIP-seq in AIPC cells. AR target gene PCDH7 was detected by real time PCR and western blot. Methylation of PCDH7 was measured by bisulfite sequencing and bisulfite amplicon sequencing. Cell growth, invasion and apoptosis were measured by CCK-8, transwell and flow cytometry, respectively. AR was significantly enriched in the upstream of PCDH7 gene. The expression of PCDH7 was significantly decreased, while the methylation of PCDH7 was increased in the AIPC cells compared to the ADPC cells. DNA methyltransferase inhibitor significantly suppressed the methylation and increased the mRNA and protein level of PCDH7. Moreover, overexpression of DNMT1 remarkably reduced the mRNA and protein level of PCDH7. DNA methyltransferase inhibitor decreased the cell growth and invasion while promote the cell apoptosis in the AIPC cells. AR significantly target PCDH7, whose hypermethylation may repress cell growth and invasion, and promote apoptosis in AIPC. This study might provide a novel potential target for the treatment of AIPC.