The dual role of RNA-binding proteins: promotion of tumorigenesis, drug resistance, and emerging therapeutic targets

Cancer is a complex and multifaceted disease characterized by a multitude of molecular factors. RNA-binding proteins (RBPs) have emerged as pivotal regulators of tumor development, progression, and chemoresistance through their interactions with target transcripts. These interactions regulate a multitude of processes, including alternative splicing, cleavage and polyadenylation, RNA localization, translation, N6-methyladenosine (m6A) RNA modification, and DNA double-strand break repair. The RBP family comprises over 2000 proteins and plays a critical role in oncogene expression, invasion, metastasis, and inhibition of apoptosis. However, the mechanisms by which RBPs selectively recognize RNAs remain an active area of research. This review examines recent advancements in understanding RNA-binding domains and the RNA processes regulated by RBPs in tumorigenesis. Notably, this study summarizes and highlights the roles of RNA-binding domains in cancers and the molecular mechanisms of RBPs in chemotherapy resistance. It also discusses the potential of targeting RBPs for cancer therapy and reviews RBPs that are dysregulated in cancers. Additionally, we highlight recently developed tools for predicting RBP-RNA binding activities to provide valuable support for ongoing research efforts.