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Dissecting the expression landscape of RNA-binding proteins in human cancers

机译:剖析人类癌症中RNA结合蛋白的表达方式

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BackgroundRNA-binding proteins (RBPs) play important roles in cellular homeostasis by controlling gene expression at the post-transcriptional level.ResultsWe explore the expression of more than 800 RBPs in sixteen healthy human tissues and their patterns of dysregulation in cancer genomes from The Cancer Genome Atlas project. We show that genes encoding RBPs are consistently and significantly highly expressed compared with other classes of genes, including those encoding regulatory components such as transcription factors, miRNAs and long non-coding RNAs. We also demonstrate that a set of RBPs, numbering approximately 30, are strongly upregulated (SUR) across at least two-thirds of the nine cancers profiled in this study. Analysis of the protein–protein interaction network properties for the SUR and non-SUR groups of RBPs suggests that path length distributions between SUR RBPs is significantly lower than those observed for non-SUR RBPs. We further find that the mean path lengths between SUR RBPs increases in proportion to their contribution to prognostic impact. We also note that RBPs exhibiting higher variability in the extent of dysregulation across breast cancer patients have a higher number of protein–protein interactions. We propose that fluctuating RBP levels might result in an increase in non-specific protein interactions, potentially leading to changes in the functional consequences of RBP binding. Finally, we show that the expression variation of a gene within a patient group is inversely correlated with prognostic impact.ConclusionsOverall, our results provide a roadmap for understanding the impact of RBPs on cancer pathogenesis.
机译:背景RNA结合蛋白(RBPs)通过控制转录后水平的基因表达在细胞稳态中发挥重要作用。结果我们探索了16种健康人体组织中800多种RBPs的表达及其在癌症基因组癌症基因组中的失调模式。 Atlas项目。我们显示,与其他类别的基因(包括那些编码调控成分,例如转录因子,miRNA和长非编码RNA)相比,编码RBPs的基因始终且显着高表达。我们还证明,在本研究中介绍的九种癌症中,至少有三分之二的一组RBP约有30种被强烈上调(SUR)。对RUR的SUR和非SUR组的蛋白质间相互作用网络特性的分析表明,SUR RBP之间的路径长度分布显着低于非SUR RBP所观察到的路径长度分布。我们进一步发现,SUR RBP之间的平均路径长度与它们对预后影响的贡献成正比。我们还注意到,在乳腺癌患者中异常调节程度方面表现出较高变异性的RBP具有更高数量的蛋白质相互作用。我们建议波动的RBP水平可能会导致非特异性蛋白质相互作用的增加,可能导致RBP结合功能后果的变化。最后,我们证明了患者组中基因的表达变异与预后影响呈负相关。结论总体而言,我们的结果为了解RBP对癌症发病机理的影响提供了路线图。

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