Wan Xuechao, Yang Shu, Huang Wenhua, Wu Denglong, Chen Hongbing, Wu Ming, Li Junliang, Li Tao, Li Yao
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, People's Republic of China.
Department of Urology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, People's Republic of China.
J Exp Clin Cancer Res. 2016 Feb 17;35:34. doi: 10.1186/s13046-016-0308-0.
Biochemical recurrence (BCR) is widely used to define the treatment success and to make decisions on if or how to initiate a secondary therapy, but uniform criteria to define BCR after radical prostatectomy (RP) is not yet completely assessed. UHRF1 has a unique function in regulating the epigenome by linking DNA methylation with histone marks. The clinical value of UHRF1 in PCa has not been well done. Therefore, we evaluated the prognostic significance of UHRF1.
UHRF1 expression in PCa cells was monitored by qRT-PCR and Western blot analyses. UHRF1 expression was knocked down using specific siRNAs, and the effects of knockdown on the proliferation, migration, cell cycle, and apoptosis of PCa cell lines were investigated. UHRF1 protein expression was evaluated in 225 PCa specimens using immunohistochemistry in tissue microarrays. Correlations between UHRF1 expression and the clinical features of PCa were assessed.
The results showed that UHRF1 was overexpressed in almost all of the PCa cell lines. In PCa cells, UHRF1 knockdown inhibited cell proliferation and migration, and induced apoptosis. UHRF1 expression levels were correlated with some clinical features of PCa. Multivariate analysis showed that UHRF1 expression was an independent prognostic factor for biochemical recurrence-free survival.
UHRF1 functions as an oncogene in prostate cancer and appears to be capable of predicting the risk of biochemical recurrence in PCa patients after radical prostatectomy, and may serve as a potential therapeutic target for PCa.
生化复发(BCR)被广泛用于定义治疗效果,并决定是否或如何启动二次治疗,但前列腺癌根治术(RP)后定义BCR的统一标准尚未得到充分评估。UHRF1在通过将DNA甲基化与组蛋白标记联系起来调节表观基因组方面具有独特功能。UHRF1在前列腺癌中的临床价值尚未得到充分研究。因此,我们评估了UHRF1的预后意义。
通过qRT-PCR和蛋白质印迹分析监测前列腺癌细胞中UHRF1的表达。使用特异性小干扰RNA(siRNA)敲低UHRF1表达,并研究敲低对前列腺癌细胞系增殖、迁移、细胞周期和凋亡的影响。在组织芯片中使用免疫组织化学评估225例前列腺癌标本中UHRF1蛋白的表达。评估UHRF1表达与前列腺癌临床特征之间的相关性。
结果显示,几乎所有前列腺癌细胞系中UHRF1均过表达。在前列腺癌细胞中,敲低UHRF1可抑制细胞增殖和迁移,并诱导凋亡。UHRF1表达水平与前列腺癌的一些临床特征相关。多变量分析表明,UHRF1表达是无生化复发生存的独立预后因素。
UHRF1在前列腺癌中起癌基因作用,似乎能够预测前列腺癌根治术后患者生化复发的风险,并且可能成为前列腺癌的潜在治疗靶点。