Cancer the'RBP'eutics-RNA-binding proteins as therapeutic targets for cancer

Abstract

RNA-binding proteins (RBPs) play a critical role in the regulation of various RNA processes, including splicing, cleavage and polyadenylation, transport, translation and degradation of coding RNAs, non-coding RNAs and microRNAs. Recent studies indicate that RBPs not only play an instrumental role in normal cellular processes but have also emerged as major players in the development and spread of cancer. Herein, we review the current knowledge about RNA binding proteins and their role in tumorigenesis as well as the potential to target RBPs for cancer therapeutics.

Keywords: Aptamer; Cancer therapeutics; Peptide; RNA-binding domains; RNA-binding proteins; Small molecules; siRNA.

Figure 1

Schematic representation of RNA-binding proteins (RBPs) with various RNA-binding domains (RBDs). Each RBD is drawn as colored boxes and their lengths are shown according to their actual sizes (aa, amino acids). The common RBDs include: CSD, cold shock domain; dsRBD, double-stranded RNA-binding domain; KH, K-homology domain; La motif; PAZ, Piwi/Argonaute/Zwille domain; Piwi domain; RRM, RNA-recognition motif; ZnF, zinc fingers of the CCHC, CCCH, and ZZ type.

Figure 2

Strategies that are being applied to target RBPs for cancer therapeutics. Small-molecules can be designed to inhibit the interaction of RBP with an RNA, suppress RBP’s enzymatic activity, block RBP post-translational modification (PTM), or induce RBP degradation. The Peptides-based strategy can be designed to hinder the RBP association with its functional partner(s). The oligonucleotide-based strategies include ASO, siRNA, and Aptamer, which can either mediate RBP mRNA degradation or inhibit RBP-RNA interaction. In addition, two potential strategies are included, natural or artificial circular RNAs- or CRISPR-based approaches. Circular RNAs can be designed to bind RBDs of RBPs and compete out target RNAs. CRISPR based approaches can be used to create oncogenic RBP knockout/knockin (to correct cancer-specific mutation in RBP or RBP binding sites). RISC, RNA-induced silencing complex.