Regulatory mechanism of androgen receptor on NCAPD3 gene expression in prostate cancer

Yingying Yin  ¹ , Qianmei Liu  ¹ , Yingying Shao  ¹ , Xinyuan He  ¹ , Qingyi Zhu  ² , Shan Lu  ¹ , Ping Liu  ¹ Affiliations

• PMID: 34591337
• DOI: 10.1002/pros.24245

Abstract

Background: Androgen receptor (AR) is an essential transcriptional factor that contributes to the development and progression of prostate cancer (PCa). NCAPD3 is a component of the condensin II complex and plays a critical role in cell mitosis by regulating chromosome condensation; however, the relationship between NCAPD3 and AR remains unknown.

Methods: Transcriptome sequencing assay is carried out to analyze the expression of the NCAP family in clinic samples. Chromatin immunoprecipitation (ChIP) sequencing, ChIP assay, and dual-luciferase assay are used to identify the androgen-responsive element in NCAPD3 enhancer. Immunohistochemistry, quantitative reverse transcription-polymerase chain reaction, and western-blot assay are employed to check the expression of genes in PCa tissues and in PCa cells. Confocal immunofluorescence microscopy analysis is used for identifying the regulation of AR on NCAPD3-mediated chromosome condensation. Colony formation, cell cycle assay, wound healing assay, and transwell experiments are used to explore the regulation of AR on the functions of NCAPD3. In vivo experiment is employed to identify in vitro experimental results.

Results: NCAPD3 is an androgen/AR axis-targeted gene and is involved in AR-induced PCa cell proliferation, migration, and invasion in vitro and in vivo. Androgen treatment and AR overexpression increase the expression of NCAPD3 in PCa cell lines. The canonical exist in the enhancer region of NCAPD3. Androgen/AR axis regulates NCAPD3-invovled chromosome condensation during cell mitosis.

Conclusions: Our report demonstrated that NCAPD3 is an androgen-responsive gene and upregulated by androgen/AR axis and involved in AR-promoted progression of PCa, suggesting a potential role of NCAPD3 in the PCa development.

Keywords: NCAPD3; androgen; androgen receptor; condensin; prostate cancer.