Epigenetic modification‐dependent androgen receptor occupancy facilitates the ectopic TSPY1 expression in prostate cancer cells. Issue 2 (7th December 2020)

• Record Type: Journal Article
• Authors: Leng, Xiangyou; Liu, Mohan; Tao, Dachang; Yang, Bo; Zhang, Yangwei; He, Tianrong; Xie, Shengyu; Wang, Zhaokun; Liu, Yunqiang; Yang, Yuan
• Is Part Of: Cancer science. Volume 112:Issue 2(2021)
• Page Start: 691
• Page End: 702
• Publication Date: 2020-12-07
• Subjects: androgen -- androgen receptor -- DNA methylation -- prostate cancer -- TSPY1; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14731
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Testis‐specific protein Y‐encoded 1 ( TSPY1 ), a Y chromosome‐linked oncogene, is frequently activated in prostate cancers (PCa) and its expression is correlated with the poor prognosis of PCa. However, the cause of the ectopic transcription of TSPY1 in PCa remains unclear. Here, we observed that the methylation status in the CpG islands (CGI) of the TSPY1 promoter was negatively correlated with its expression level in different human samples. The acetyl‐histone H4 and trimethylated histone H3‐lysine 4, two post–translational modifications of histones occupying the TSPY1 promoter, facilitated the TSPY1 expression in PCa cells. In addition, we found that androgen accelerated the TSPY1 transcription on the condition of hypomethylated of TSPY1‐ CGI and promoted PCa cell proliferation. Moreover, the binding of androgen receptor (AR) to the TSPY1 promoter, enhancing TSPY1 transcription, was detected in PCa cells. Taken together, our findings identified the regulation of DNA methylation, acting as a primary mechanism, on TSPY1 expression in PCa, and revealed that TSPY1 is an androgen‐AR axis‐regulated oncogene, suggesting a novel and potential target for PCa therapy. Abstract : Our findings identify the regulation of DNA methylation, acting as a primary mechanism, on TSPY1 expression in PCa, and reveal that TSPY1 is an androgen‐AR axis‐regulated oncogene, suggesting a novel and potential target for PCa therapy.