Pan-cancer analysis of cancer-specific transcript isoforms reveals the regulatory impact of isoform switching on the alteration of the interplay between RBPs and miRNAs in cancers.

Abstract

The switch in the predominantly expressed transcript isoform of the same gene has been identified as a significant factor in the progression of various types of cancer. These switches can impact the gain or loss of different 3'UTRs, which are hotspots for the binding of microRNAs (miRNAs) and RNA-binding proteins (RBPs). In this study, we found that in cancer-specific dominant expressing transcripts, the binding of miRNA and RBP is disrupted, suggesting that transcript switching could play a part in modulating post-transcriptional gene expression during the progression and development of cancer. Our spatial correlation analysis demonstrated that changes in miRNA and RBP binding, triggered by transcript switching, could interrupt their interplay. Additionally, statistical analysis revealed that local folding energy (LFE) is a key factor in changing miRNA and RBP interactions due to isoform switching. Overall, this study revealed that changes in cancerspecific transcripts could influence miRNA-RBP interactions due to alternations in the local RNA structure of the transcript caused by isoform switching, thereby leading to the dysregulation of crucial genes involved in the evolution and progression of cancer.