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氯离子细胞内通道3和4在恶性胸膜间皮瘤中的转录过表达。

Transcriptional over-expression of chloride intracellular channels 3 and 4 in malignant pleural mesothelioma.

作者信息

Tasiopoulou Vasiliki, Magouliotis Dimitrios, Solenov Evgeniy I, Vavougios Georgios, Molyvdas Paschalis-Adam, Gourgoulianis Konstantinos I, Hatzoglou Chrissi, Zarogiannis Sotirios G

机构信息

Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa 41500, Greece.

Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia; Novosibirsk State University, Novosibirsk 630090, Russia.

出版信息

Comput Biol Chem. 2015 Dec;59 Pt A:111-6. doi: 10.1016/j.compbiolchem.2015.09.012. Epub 2015 Sep 28.

DOI:10.1016/j.compbiolchem.2015.09.012
PMID:26445368
Abstract

BACKGROUND

Chloride Intracellular Channels (CLICs) are contributing to the regulation of multiple cellular functions. CLICs have been found over-expressed in several malignancies, and therefore they are currently considered as potential drug targets. The goal of our study was to assess the gene expression levels of the CLIC's 1-6 in malignant pleural mesothelioma (MPM) as compared to controls.

METHODS

We used gene expression data from a publicly available microarray dataset comparing MPM versus healthy tissue in order to investigate the differential expression profile of CLIC 1-6. False discovery rates were calculated and the interactome of the significantly differentially expressed CLICs was constructed and Functional Enrichment Analysis for Gene Ontologies (FEAGO) was performed.

RESULTS

In MPM, the gene expressions of CLIC3 and CLIC4 were significantly increased compared to controls (p=0.001 and p<0.001 respectively). A significant positive correlation between the gene expressions of CLIC3 and CLIC4 (p=0.0008 and Pearson's r=0.51) was found. Deming regression analysis provided an association equation between the CLIC3 and CLIC4 gene expressions: CLIC3=4.42CLIC4-10.07.

CONCLUSIONS

Our results indicate that CLIC3 and CLIC4 are over-expressed in human MPM. Moreover, their expressions correlate suggesting that they either share common gene expression inducers or that their products act synergistically. FAEGO showed that CLIC interactome might contribute to TGF beta signaling and water transport.

摘要

背景

氯离子细胞内通道(CLICs)有助于调节多种细胞功能。已发现CLICs在几种恶性肿瘤中过表达,因此它们目前被视为潜在的药物靶点。我们研究的目的是评估与对照组相比,CLIC 1 - 6在恶性胸膜间皮瘤(MPM)中的基因表达水平。

方法

我们使用来自公开可用微阵列数据集的基因表达数据,比较MPM与健康组织,以研究CLIC 1 - 6的差异表达谱。计算错误发现率,并构建显著差异表达的CLICs的相互作用组,并进行基因本体功能富集分析(FEAGO)。

结果

在MPM中,与对照组相比,CLIC3和CLIC4的基因表达显著增加(分别为p = 0.001和p < 0.001)。发现CLIC3和CLIC4的基因表达之间存在显著正相关(p = 0.0008,Pearson相关系数r = 0.51)。Deming回归分析提供了CLIC3和CLIC4基因表达之间的关联方程:CLIC3 = 4.42CLIC4 - 10.07。

结论

我们的结果表明CLIC3和CLIC4在人类MPM中过表达。此外,它们的表达相关,表明它们要么共享共同的基因表达诱导物,要么它们的产物协同作用。FAEGO表明CLIC相互作用组可能有助于TGFβ信号传导和水运输。

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