Fan Wang, Chen Xiaowei, Li Caiyan, Chen Lvan, Liu Pingfei, Chen Zhijun
Department of Neurosurgery, The First People's Hospital of Jingmen, Jingmen, China.
J Cancer Res Ther. 2014 Jul-Sep;10(3):636-40. doi: 10.4103/0973-1482.138202.
Growing evidence shows that disruption of circadian rhythm may be a risk factor in the development of glioma. However, the molecular mechanisms of genes controlling circadian rhythm in glioma cells have not been explored and differential expression of the circadian clock genes in glioma and non-tumor cells may provide a molecular basis for manifesting this mechanism.
The aim of the following study is to analyze the PER2 expression involved in the pathogenesis of glioma.
Using immunohistochemical staining, methylation specific polymerase chain reaction techniques, we examined the expression of the most important clock genes, PER2, in 92 gliomas.
The association between tumor grade (high-grade/low-grade gliomas) and expression of the investigated proteins (negative/positive) was assessed using the Spearman, Chi-square test and two-sample t-test, included in the Statistical Package for the Social Science, version 13.0. Using Spearman Correlation to analyse correlation between the expression of PER 2 and PER2 promoter methylation.
Our results reveal disturbances in the expression of the period 2 (PER2) genes in most (52.17%) of the glimoa cells in comparison with the nearby non-cancerous cells and the PER2 gene deregulation is most probably by methylation of the PER2 promoter.
Since, the circadian clock controls expression of cell-cycle related genes, we suggest that disturbances in PER2 gene expression may result in disruption of the control of the normal circadian clock, thus benefiting the survival of cancer cells and promoting carcinogenesis. Differential expression of circadian genes in non-cancerous and cancerous cells may provide a molecular basis for chronotherapy of glioma.
越来越多的证据表明，昼夜节律紊乱可能是胶质瘤发生发展的一个危险因素。然而，胶质瘤细胞中控制昼夜节律的基因的分子机制尚未得到探索，胶质瘤细胞与非肿瘤细胞中生物钟基因的差异表达可能为揭示这一机制提供分子基础。
以下研究的目的是分析参与胶质瘤发病机制的PER2表达。
我们采用免疫组织化学染色、甲基化特异性聚合酶链反应技术，检测了92例胶质瘤中最重要的生物钟基因PER2的表达。
使用社会科学统计软件包第13.0版中的Spearman检验、卡方检验和两样本t检验，评估肿瘤分级（高级别/低级别胶质瘤）与所研究蛋白质表达（阴性/阳性）之间的关联。使用Spearman相关性分析PER2表达与PER2启动子甲基化之间的相关性。
我们的结果显示，与附近的非癌细胞相比，大多数（52.17%）胶质瘤细胞中周期蛋白2（PER2）基因的表达存在紊乱，PER2基因失调很可能是由于PER2启动子的甲基化。
由于生物钟控制细胞周期相关基因的表达，我们认为PER2基因表达紊乱可能导致正常生物钟控制的破坏，从而有利于癌细胞的存活并促进肿瘤发生。非癌细胞与癌细胞中昼夜节律基因的差异表达可能为胶质瘤的时辰治疗提供分子基础。
