Cheng Gong, Wang Shangqian, Li Xiao, Li Shuang, Zheng Yang, Zhang Lei, Bao Meiling, Liang Chao, Huang Zhengkai, Liu Yiyang, Qin Chao, Shao Pengfei, Li Jie, Hua Lixin, Yin Changjun, Wang Zengjun
Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Urology, the Affiliated Cancer Hospital of Jiangsu Province of Nanjing Medical University, Nanjing, China.
Oncotarget. 2016 Aug 31;8(38):64427-64439. doi: 10.18632/oncotarget.11749. eCollection 2017 Sep 8.
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 . 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.
NR6A1/CT150作为一种孤儿受体，是癌-睾丸（CT）抗原家族的一个新成员。在此，我们研究了NR6A1在接受根治性前列腺切除术的前列腺癌（PCa）患者中的表达、功能及其潜在机制。在组织芯片（TMA）中对303例根治性前列腺切除术后的前列腺癌病例进行分析，以检测基于免疫组化的NR6A1蛋白表达。采用Kaplan-Meier/log-rank分析和Cox回归分析来研究PCa中NR6A1表达与临床病理因素之间的关系。通过逆转录-聚合酶链反应（RT-PCR）检测NR6A1 mRNA表达。利用小干扰RNA介导的基因沉默敲低NR6A1以及通过慢病毒过表达NR6A1，以研究其在前列腺癌细胞中的潜在作用。PCa患者中NR6A1蛋白表达为29.7%（90/303），mRNA表达为28.1%（9/32）。NR6A1表达与 Gleason评分（GS）（P = 0.003）和肿瘤分期（P = 0.042）显著相关。NR6A1表达阳性的患者无生化复发生存期较短。NR6A1在单因素（P = 0.0159）和多因素模型（P = 0.0317）中均能预测生化复发。此外，NR6A1基因沉默导致G0/G1期细胞周期阻滞，并降低前列腺癌细胞DU145和PC3的转移和侵袭潜能。相反，NR6A1过表达减少G0/G1期细胞周期阻滞，并促进前列腺癌细胞22RV1的转移和侵袭潜能。并且NR6A1过表达显著促进肿瘤生长。更重要的是，下调NR6A1可逆转DU145和PC3细胞系中的上皮-间质转化（EMT）过程，而过表达则可增强22RV1细胞系中的EMT过程。NR6A1在PCa细胞的迁移和侵袭中起重要作用，表明NR6A1可能作为根治性前列腺切除术后生化复发的一个新标志物。
