RNA Binding Protein as an Emerging Therapeutic Target for Cancer Prevention and Treatment

Abstract

After transcription, RNAs are always associated with RNA binding proteins (RBPs) to perform biological activities. RBPs can interact with target RNAs in sequence- and structure-dependent manner through their unique RNA binding domains. In development and progression of carcinogenesis, RBPs are aberrantly dysregulated in many human cancers with various mechanisms, such as genetic alteration, epigenetic change, noncoding RNA-mediated regulation, and post-translational modifications. Upon deregulation in cancers, RBPs influence every step in the development and progression of cancer, including sustained cell proliferation, evasion of apoptosis, avoiding immune surveillance, inducing angiogenesis, and activating metastasis. To develop therapeutic strategies targeting RBPs, RNA interference-based oligonucleotides or small molecule inhibitors have been screened based on reduced RBP-RNA interaction and changed level of target RNAs. Identification of binding RNAs with high-throughput techniques and integral analysis of multiple datasets will help us develop new therapeutic drugs or prognostic biomarkers for human cancers.

Keywords: Cancer; Chemoprevention; RNA-binding proteins; Therapeutics.

Figure 1

Schematic diagram for various RNA binding domains of RNA binding proteins (RBPs). RBP interacts with target mRNAs using unique RNA binding domain (RBD) or a combination of different RBDs. Depending on RBDs, each RBP has specificity and affinity for its target RNAs. Each domain is schematically depicted with different shapes and colors. Each RBP is presented depending on its size. dsRBM, double-stranded RNA binding motiff; hnRNP, heterogeneous nuclear ribonucleoprotein; RRM, RNA recognition motif; KH, K-homology; ZF-ZZ, zinc finger binding with two zinc ions; ZF-CCCH, zinc finger C-x8-C-x5-C-x3-H type; PKR, protein kinase R; hnRNPA1, heterogeneous ribonucleoprotein A1; HuR, Hu-antigen R; U2AF35, U2 small nuclear RNA auxiliary factor 35; SAM68, Src-associated protein in mitosis of 68 kDa; TTP, tristetraprolin; IGF2BPs, Insulin-like growth factor 2 mRNA-binding proteins; CPEB4, cytoplasmic polyadenylation element binding protein 4; AA, amino acids.