Comprehensive Genomic Characterization of RNA-Binding Proteins across Human Cancers

Abstract

Summary: RNA-binding proteins (RBPs) regulate the expression of thousands of transcripts, and some are reported to be involved in human tumorigenesis. However, little is known about the dysregulation of RBPs at the genomic level in human cancers. Here, we conducted comprehensive analyses for expression, somatic copy number alteration (SCNA), and mutation profiles of 1,542 RBPs in ∼7,000 clinical specimens across 15 cancer types. We identified markedly dysregulated RBPs and found that downregulation was a predominant pattern in cancer. Combined with recurrent SCNA data, we identified 76 RBPs as potential drivers. We also discovered a set of 139 RBPs that were significantly mutated in cancers. We confirmed the oncogenic property of six RBPs in colorectal and liver cancer cell lines by using in vitro functional experiments. Our study highlights the potential roles of RBPs in carcinogenesis and lays the groundwork to better understand the functions and mechanisms of RBPs in cancer. : Wang et al. characterize transcriptional and genomic alterations in the landscape of RNA-binding proteins (RBPs) in ∼7,000 clinical samples across 15 human cancer types and experimentally validate the effects of several cancer-related RBPs on cell viability. Keywords: RNA-binding proteins, dysregulation, somatic copy number alterations, mutation profile, cancer driver