摘要
Transcription factors, which represent an important class of proteins that play key roles in controlling cellular proliferation and cell cycle modulation, are attractive targets for cancer therapy. Previous researches have shown that the expression level of activating transcription factor 5 （ATF5） was frequently increased in glioma and its acetylation level was related to glioma. The purposes of this study were to explore the methylation level of ATF5 in clinical glioma tissues and to explore the effect of ATF5 methylation on the expression of ATF5 in glioma. Methylation of the promoter region of ATF5 was assayed by bisulflte-specific polymerase chain reaction （PCR） sequencing analysis in 35 cases of glioma and 5 normal tissues. Quantitative real-time PCR （qRT-PCR） was also performed to detect ATF5 mRNA expression in 35 cases of glioma and 5 normal tissues. Clinical data were collected from the patients and analyzed. The percentages of methylation of the ATF5 gene in the promoter region in healthy control, patients with well-differentiated glioma, and those with poorly differentiated glioma were 87.78%, 73.89%, and 47.70%, respectively. Analysis of the methylation status of the promoter region of the ATF5 gene showed a gradually de- creased methylation level in poorly differentiated glioma, well-differentiated glioma, and normal tissues （P〈0.05）. There was also a significant difference between well-differentiated glioma and poorly differentiated glioma （P〈0.05）. ATF5 mRNA expression in glioma was significantly higher than that in the normal tissues （P〈0.05）. This study provides the first evidence that the methylation level of ATF5 decreased, and its mRNA expression was evidently up-regulated in glioma.
目的:研究临床胶质瘤标本中激活转录因子5(ATF5)启动子区CpG岛甲基化状态及临床意义。创新点:首次发现在胶质瘤标本中ATF5的甲基化水平下调,其表达水平下调。方法:收集35临床胶质瘤组织及5例急性脑外伤组织作为对照,应用亚硫酸盐测序技术检测ATF5的甲基化水平,并结合临床病理资料进行分析;实时荧光定量聚合酶链式反应(qRT-PCR)检测所有标本中ATF5 mRNA的表达水平变化。结论:5例正常脑组织、10例低级别胶质瘤及25例高级别胶质瘤的甲基化比例分别为87.78%、73.89%和47.70%(图2),两组相比差异有统计学意义(P<0.05;图3a和3b);qRT-PCR结果表明,与对照相比,胶质瘤标本中ATF5表达水平上升(P<0.05;图3d)。综上所述,胶质瘤组织中ATF5基因启动子区CpG岛的甲基化状态对该基因的表达有重要意义。
基金
supported by the National Natural Science Foundation(Nos.81471958 and 31401258)
the Natural Science Foundation of Shandong Province(No.ZR2012BM006),China
