Cheng Huan, Deng Zhonglei, Wang Zengjun, Zhang Wei, Su Jiantang
Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
J Biomed Res. 2012 Sep;26(5):319-24. doi: 10.7555/JBR.26.20110099. Epub 2011 Apr 12.
The purpose of this study was to determine the relationship between hypermethylation of DACT1 gene promoter and lower mRNA expression in bladder urothelial carcinoma tissue. The methylation status of 29 urothelial carcinoma samples and 29 normal tissue samples were examined by methylation-specific polymerase chain reaction (MSP). The DACT1 mRNA transcript levels and DACT1 protein levels in all samples were then evaluated to define the relationship between the methylation status of the DACT1 promoter and its expression at the transcriptional and translational levels. Decreased expression of DACT1 was detected in 89.66% of urothelial carcinomas (26/29; P < 0.005). Promoter hypermethylation was found in 58.62% (17/29) urothelial carcinomas and 25% (7/29) normal tissues, respectively (P < 0.05). DACT1 expression was lower in tissues where the DACT1 gene promoter was hypermethylated than in unmethylated tissues (0.25±0.17 vs 0.69±0.30, P < 0.05). DACT1 gene hypermethylation was closely related to tumor size, grade and stage (P < 0.05). Our results indicate that silencing and downregulation of DACT1 mRNA may be implicated in carcinogenesis and the progression of bladder urothelial carcinoma, and may be a potential prognostic factor.
本研究的目的是确定膀胱尿路上皮癌组织中DACT1基因启动子高甲基化与较低的mRNA表达之间的关系。采用甲基化特异性聚合酶链反应（MSP）检测29例尿路上皮癌样本和29例正常组织样本的甲基化状态。然后评估所有样本中DACT1 mRNA转录水平和DACT1蛋白水平，以确定DACT1启动子甲基化状态与其在转录和翻译水平表达之间的关系。在89.66%的尿路上皮癌（26/29；P<0.005）中检测到DACT1表达降低。分别在58.62%（17/29）的尿路上皮癌和25%（7/29）的正常组织中发现启动子高甲基化（P<0.05）。DACT1基因启动子高甲基化的组织中DACT1表达低于未甲基化组织（0.25±0.17对0.69±0.30，P<0.05）。DACT1基因高甲基化与肿瘤大小、分级和分期密切相关（P<0.05）。我们的结果表明，DACT1 mRNA的沉默和下调可能与膀胱尿路上皮癌的发生和进展有关，可能是一个潜在的预后因素。
