Circular RNAs in cancer: novel insights into origins, properties, functions and implications

Circular RNAs (circRNAs) are a large class of RNAs that, unlike linear RNAs, form covalently closed continuous loops and have recently shown huge capabilities as gene regulators in mammals. These circRNAs mainly arise from exons or introns, and are differentially generated by back splicing or lariat introns. Interestingly, they are found to be enormously abundant, evolutionally conserved and relatively stable in cytoplasm. These features confer numerous potential functions to circRNAs, such as acting as microRNA (miRNA) sponges, binding to RNA-associated proteins to form RNA-protein complexes and then regulating gene transcription. Importantly, circRNAs associate with cancer-related miRNAs and the circRNA-miRNA axes are involved in cancer-related pathways. Some synthetic circRNAs have shown the remarkable anti-cancer effects. Though circRNAs are ancient molecules, the huge therapeutic potentials of circRNAs are recently being discovered from the laboratory to the clinic. Here, we review the current understanding of the roles of circRNAs in cancers and the potential implications of circRNAs in cancer targeted therapy.