Relationship between differentially expressed mRNA and mRNA-protein correlations in a xenograft model system
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Differential mRNA expression studies implicitly assume that changes in mRNA expression have biological meaning, most likely mediated by corresponding changes in protein levels. Yet studies into mRNA-protein correspondence have shown 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.
Koussounadis , A , Langdon , S , Um , I H , Harrison , D J & Smith , V A 2015 , ' Relationship between differentially expressed mRNA and mRNA-protein correlations in a xenograft model system ' Scientific Reports , vol 5 , 10775 . DOI: 10.1038/srep10775
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This work was supported by Medical Research Scotland (FRG353 to VAS), the FP7- Directorate-General for Research and Innovation of the European Commission (EU HEALTHF4-2012-305033 to Coordinating Action Systems Medicine to DJH); the Chief Scientist Office of Scotland (to DJH) and the Scottish Funding Council (to DJH and SPL).
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