Dissecting the expression landscape of RNA-binding proteins in human cancers
1 Department of Biohealth Informatics, School of Informatics and Computing, Indiana University – Purdue University, 719 Indiana Ave Ste 319, Walker Plaza Building, Indianapolis, IN 46202, USA
2 Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 5021 Health Information and Translational Sciences (HITS), 410 West 10th Street, Indianapolis, IN 46202, USA
3 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Medical Research and Library Building, 975 West Walnut Street, Indianapolis, IN 46202, USA
Genome Biology 2014, 15:R14 doi:10.1186/gb-2014-15-1-r14Published: 10 January 2014
RNA-binding proteins (RBPs) play important roles in cellular homeostasis by controlling gene expression at the post-transcriptional level.
We 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.
Overall, our results provide a roadmap for understanding the impact of RBPs on cancer pathogenesis.