Glioblastoma and calcium signaling--analysis of calcium toolbox expression.

N. Robil, F. Petel, M. Kilhoffer, J. Haiech
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引用次数: 21

Abstract

The characteristics of a cellular calcium signal (calcium signature) are determined, at least partly, by the expression of a subset of genes encoding proteins involved in calcium entry, calcium uptake and calcium modulation. Our aim in the present work was to characterize the set of genes involved in calcium signal generation that are differentially expressed in normal brain tissues versus brain tumor and/or glioma stem cells. Public datasets were analyzed according to a four step methodology consisting of: 1. detecting the outliers by using principal component analysis of the whole transcriptome; 2. building a calcium toolbox composed of 260 genes involved in the generation and modulation of the calcium signal; 3. analyzing the calcium toolbox transcriptome of different human brain areas and 4. detecting genes from the calcium toolbox preferentially expressed in tumor tissues or tumor cells compared to normal brain tissues. Our approach was validated on normal brain tissue. Tumor sample analysis allowed us to disclose a set of eighteen genes characteristic of glioblastoma tissues or glioma stem cells. Interpreting the set of genes highlighted in the study led us to propose that i) the mechanism of store operated calcium entry is strongly perturbed in cancer cells and tissues, ii) the process of calcium reuptake into mitochondria is more important in cancer cells and tissues than in their normal counterparts and iii) these two mechanisms may be coupled in at least one subgroup of the glioblastoma stem cells.
胶质母细胞瘤与钙信号传导——钙工具箱表达分析。
细胞钙信号的特征(钙信号)至少部分是由编码钙进入、钙摄取和钙调节的蛋白质的基因子集的表达决定的。我们目前工作的目的是表征一组参与钙信号产生的基因,这些基因在正常脑组织与脑肿瘤和/或胶质瘤干细胞中表达差异。公共数据集的分析采用四步方法,包括:1。利用全转录组主成分分析检测异常值;2. 构建由260个参与钙信号产生和调控的基因组成的钙工具箱;3.4.不同脑区钙工具箱转录组分析。检测与正常脑组织相比,在肿瘤组织或肿瘤细胞中优先表达的钙工具箱基因。我们的方法在正常脑组织上得到了验证。肿瘤样本分析使我们能够揭示一组胶质母细胞瘤组织或胶质瘤干细胞的18个基因特征。对研究中强调的一组基因的解释使我们提出:i)储存操作的钙进入机制在癌细胞和组织中受到强烈干扰;ii)钙再摄取到线粒体的过程在癌细胞和组织中比在正常细胞和组织中更重要;iii)这两种机制可能在胶质母细胞瘤干细胞的至少一个亚群中耦合。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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