NR6A1/CT150, as an orphan receptor, is a novel member of the
cancer-testis (CT)
antigen family. Here, we investigated the expression and function of NR6A1 and its underlying mechanisms in
prostate cancer (PCa) patients who underwent radical
prostatectomy. A total of 303 cases of
prostate cancer after radical
prostatectomy were analysed in a tissue microarray (TMA) for NR6A1 immunohistochemistry-based
protein expression. Kaplan-Meier/log-rank analysis and Cox regression analysis were used to investigate the relationship between NR6A1 expression and clinicopathological factors in PCa. NR6A1
mRNA expression was examined by reversing
transcriptase-polymerase chain reaction (RT-PCR). Knockdown of NR6A1 by
small interfering RNA mediated gene silencing and overexpression of NR6A1 through lentivirus were utilized to investigate its potential role in
prostate cancer cells. NR6A1
protein expression was 29.7% (90/303) and
mRNA expression was 28.1%(9/32) in PCa patients. NR6A1 expression was significantly associated with Gleason score (GS) (P=0.003) and
tumor stage (P=0.042). The patients with positive NR6A1 expression have a shorter biochemical recurrence-free survival. NR6A1 predicted biochemical recurrence in univariate (P=0.0159) and multivariate models (P=0.0317). In addition, gene silencing of NR6A1 resulted in G0/G1 phase cell cycle arrest, and decreased metastatic and invasive potential of
prostate cancer cells DU145 and PC3. In contrast, overexpression of NR6A1 reduced G0/G1 phase cell cycle arrest, and promoted metastatic and invasive potential of
prostate cancer cells 22RV1. And overexpression of NR6A1 significantly promoted
tumor growth in vivo. What's more, down regulation of NR6A1 could reverse epithelial-to-mesenchymal transition (EMT) process in DU145 and PC3 cell lines, and the overexpression could enhance EMT process in 22RV1 cell line. NR6A1 played a prominent role in migration and invasion of PCa cells, and it is indicated that NR6A1 may act as a novel marker for biochemical recurrence after radical
prostatectomy.