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Relationship between differentially expressed mRNA and mRNA-protein correlations in a xenograft model system

机译:异种移植模型系统中差异表达的mRNA和mRNA-蛋白质相关性之间的关系

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摘要

Differential mRNA expression studies implicitly assume that changes in mRNAexpression have biological meaning, most likely mediated by correspondingchanges in protein levels. Yet studies into mRNA-protein correspondence haveshown notoriously poor correlation between mRNA and protein expression levels, creating concern for inferences from only mRNA expression data. However, none of these studies have examined in particular differentially expressed mRNA. Here, we examined this question in an ovarian cancer xenograft model. We measured protein and mRNA expression for twenty-nine genes in four drug-treatment conditions and in untreated controls. We identified mRNAs differentially expressed between drug-treated xenografts and controls, then analysed mRNA-protein expression correlation across a five-point time-course within each of the four experimental conditions. We evaluated correlations between mRNAs and their protein products for mRNAs differentially expressed within an experimental condition compared to those that are not. We found that differentially expressed mRNAs correlate significantly better with their protein product than non-differentially expressed mRNAs. This result increases confidence for the use of differential mRNA expression for biological discovery in this system, as well as providing optimism for the usefulness of inferences from mRNA expression in general.
机译:差异性mRNA表达研究隐含地假设mRNA表达的变化具有生物学意义,最有可能是由蛋白质水平的相应变化介导的。然而,对mRNA与蛋白质的对应关系的研究显示,众所周知,mRNA与蛋白质表达水平之间的相关性很差,这引起人们仅根据mRNA表达数据进行推断的担忧。然而,这些研究都没有特别检查差异表达的mRNA。在这里,我们在卵巢癌异种移植模型中研究了这个问题。我们在四种药物治疗条件下和未治疗的对照中测量了29个基因的蛋白质和mRNA表达。我们鉴定了在药物处理的异种移植物和对照之间差异表达的mRNA,然后在四个实验条件中的每一个中的五点时间过程中分析了mRNA-蛋白质表达的相关性。我们评估了在不存在实验条件下差异表达的mRNA的mRNA及其蛋白产物之间的相关性。我们发现差异表达的mRNA与它们的蛋白质产物相关性明显好于非差异表达的mRNA。该结果增加了将差异mRNA表达用于该系统中的生物学发现的信心,并且总体上提供了对从mRNA表达进行推断的有用性的乐观态度。

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