Comprehensive analysis of the RBP regulome reveals functional modules and drug candidates in liver cancer

Abstract

Abstract RNA binding proteins (RBPs) are essential components of the transcriptomic regulome. Understanding the RBP regulome in cancer cells is crucial for uncovering carcinogenesis mechanisms and identifying novel therapeutic targets. In this study, we aimed to reveal the regulome of liver cancer upon specific perturbations. To achieve this, we applied a consensus Gene Regulatory Network (GRN) approach using knockdown data focusing on the liver cancer cell line HepG2. By integrating multiple GRNs inferred from diverse computational methods, we constructed a comprehensive regulatory network. To validate our findings, we evaluated the consensus GRN by focusing on characterizing key regulatory interactions in liver cancer. We used eCLIP-seq and RAP-seq data to verify RBP interactions and binding sites. In addition, we performed an enrichment analysis of network modules and in silico drug repurposing based on the inferred GRN. Taken together, our findings highlight the critical role of RBP-mediated regulation in liver cancer, which can be used to improve treatment strategies and develop further research.