Integrated In Silico Analyses Identify PUF60 and SF3A3 as New Spliceosome-Related Breast Cancer RNA-Binding Proteins.

Abstract

Simple SummaryGlobally, breast cancer (BC) is the most common cancer in women. Although numerous studies have attempted to address this worldwide health problem, it has not yet been possible to understand cancer in its entirety, mainly because most of the investigations have been focused on traditional molecular traits of DNA. Thus, new characteristics of breast tumorigenesis must be tackled, such as RNA-binding proteins (RBPs), which are crucial regulators of important cellular processes. To identify novel breast cancer RNA-binding proteins, we integrated several bioinformatic resources derived from experimentation on BC patient samples and cell lines. Consequently, we identified five putative breast cancer RNA-binding proteins (PUF60, TFRC, KPNB1, NSF, and SF3A3) showing strong tumorigenic characteristics. Supplementary investigation of the molecular and cellular functions of these proteins identified PUF60 and SF3A3 as new spliceosome-related breast cancer RNA-binding proteins. Further experimentation should center on these five RBPs to identify their role in breast tumorigenesis and potentially discover new druggable targets.More women are diagnosed with breast cancer (BC) than any other type of cancer. Although large-scale efforts have completely redefined cancer, a cure remains unattainable. In that respect, new molecular functions of the cell should be investigated, such as post-transcriptional regulation. RNA-binding proteins (RBPs) are emerging as critical post-transcriptional modulators of tumorigenesis, but only a few have clear roles in BC. To recognize new putative breast cancer RNA-binding proteins, we performed integrated in silico analyses of all human RBPs (n = 1392) in three major cancer databases and identified five putative BC RBPs (PUF60, TFRC, KPNB1, NSF, and SF3A3), which showed robust oncogenic features related to their genomic alterations, immunohistochemical changes, high interconnectivity with cancer driver genes (CDGs), and tumor vulnerabilities. Interestingly, some of these RBPs have never been studied in BC, but their oncogenic functions have been described in other cancer types. Subsequent analyses revealed PUF60 and SF3A3 as central elements of a spliceosome-related cluster involving RBPs and CDGs. Further research should focus on the mechanisms by which these proteins could promote breast tumorigenesis, with the potential to reveal new therapeutic pathways along with novel drug-development strategies.