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Siqi Xu,Xiaoyan Wu,Zhihua Tao,Hongsheng Li1,Chenliang Fan,Songjin Chen,Jianwei Guo,Yao Ning,Xuqi Hu 한국유전학회 2020 Genes & Genomics Vol.42 No.3
Background 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. Objective Here we aimed to identify the androgen receptor (AR) target gene and its roles in AIPC. Methods 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. Results 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. Conclusions This study might provide a novel potential target for the treatment of AIPC.