Translation role of circRNAs in cancers

Abstract

Circular RNAs (circRNAs) constitute a class of covalently closed RNA molecules. With the continuous advancement of high-throughput sequencing technology and bioinformatics tools, many circRNAs have been identified in various human tissues and cell lines. Notably, recent studies have indicated that some circRNAs have translational functions. Internal ribosome entry sites and the N6-methyladenosine modification mediate cap-independent translation. This review describes these two translation mechanisms and verification methods at the molecular level. Databases (including ORF Finder, Pfam, BLASTp, CircRNADb, CircBase, CircPro, CircCode, IRESite, IRESbase) were used to analyze whether circRNAs have the structural characteristic of translation. CircRNA minigene reporter system containing green fluorescent protein (GFP) confirmed the translation potential of circRNAs. Also, we briefly summarize the roles of proteins/peptides encoded by circRNAs (circFBXW7, circFNDC3B, circLgr4, circPPP1R12A, circMAPK1, circβ-catenin, circGprc5a, circ-SHPRH, circPINTexon2, circAKT3) that have been verified thus far in human cancers (triple-negative breast cancer, colon cancer, gastric cancer, hepatocellular carcinoma, bladder cancer, glioblastoma). Those findings suggest circRNAs have a great implication in translation of the human genome.

Keywords: N6-methyladenosine; cancers; circular RNAs; internal ribosome entry sites; translation.