Dysregulated transcription across diverse cancer types reveals the importance of RNA-binding protein in carcinogenesis

Background: It is well known that carcinogenesis is in part dictated by dysregulated transcription events and signal pathways. Large-scale transcriptional profiling studies in each cancer type have reported aberrant gene expression associated with cancer development. However, common and specific patterns altered across cancer types, especially the contribution of transcriptional and post-transcriptional regulators, are rarely explored. Results: Using transcriptional profiles from matched tumor and normal samples in the Cancer Genome Atlas pan-cancer dataset, we performed a comprehensive analysis on the altered expression across 9 cancer types, focusing on transcriptional and post-transcriptional regulators and cancer-related genes. As we expected, the transcription of cancer-related genes was significantly deregulated in tumor vs. normal across all cancer types. Surprisingly, the expression of RNA-binding proteins (RBPs), master regulators of post-transcriptional gene expression, was also significantly changed across most studied cancer types. Although the expression of RBPs was not as strongly deregulated as cancer-related genes, their direct interaction partners are enriched by cancer-related genes, suggesting the cascade regulation effect of RBPs. Integrating genetic and epigenetic profiles found that deregulated RBPs were frequently caused by genetic rather than epigenetic alterations. Furthermore, tissue-specific genes were under-expressed in tumor vs. normal across all cancer types except prostate cancer. Conclusions: Dysregulated transcription across cancer types reveals the importance of RBPs in carcinogenesis. The aberrant expression of RBPs is caused by genetic alterations and spreads their effect to cancer-related genes. In addition, disruption of tissue-specific genes contributes to the corresponding cancer pathology.