NCAPD3 promotes prostate cancer progression by up-regulating EZH2 and MALAT1 through STAT3 and E2F1

• Published in: Cellular signalling 2022-04, Vol.92, p.110265-110265, Article 110265
• Main Authors: Jing, Zuolei, Liu, Qianmei, Xie, Wanlin, Wei, Yong, Liu, Jiale, Zhang, Yi, Zuo, Wenren, Lu, Shan, Zhu, Qingyi, Liu, Ping
• Format: Article
• Language: English
• Subjects: Cell Cycle Proteins - metabolism; Cell Line, Tumor; E2F1; E2F1 Transcription Factor - genetics; Enhancer of Zeste Homolog 2 Protein - genetics; Enhancer of Zeste Homolog 2 Protein - metabolism; EZH2; Gene Expression Regulation, Neoplastic; Humans; MALAT1; Male; NCAPD3; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; STAT3; STAT3 Transcription Factor - metabolism
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2022.110265

NCAPD3 is one of the non-SMC regulatory subunits of Condensin II, which is mainly responsible for the condensation and segregation of chromosomes during mitosis. However, its role in cancer especially in prostate cancer (PCa) and the molecular mechanism have not been clearly elucidated. Here, we find that NCAPD3 is high-expression and up-regulates the levels of EZH2 and MALAT1 in PCa. In detail, high expression of NCAPD3 increases the levels of transcription factor STAT3 and E2F1 and recruits more STAT3 and E2F1 to the promoter of EZH2 gene and more STAT3 to the promoter of MALAT1 gene, and then results in the increasing expression of both EZH2 and MALAT1 in PCa cells. In vitro and in vivo functional characterization reveals that overexpression of NCAPD3 enhances the growth of PCa cells, while knockdown of NCAPD3 impairs the growth of PCa cells. Together, our data demonstrate that NCAPD3 is a tumor-promoting factor which enhances the progression of PCa by up-regulating EZH2 and MALAT1. •Higher expression of NCAPD3 promotes PCa progression.•NCAPD3 promoted cell proliferation via the regulation of STAT3/E2F1-EZH2 and STAT3-MALAT1 axis both in vitro and in vivo.•NCAPD3 regulated AR activity via EZH2 in PCa.