The emerging functions and roles of circular RNAs in cancer

Circular RNAs (circRNAs) are a class of single-stranded closed RNA molecules that undergo a specific backsplicing from pre-mRNA. With the application of high-throughput sequencing and bioinformatics, circRNAs are found to be widely expressed across species. Some functionally characterized circRNAs have critical roles in gene regulation through various actions, including sponging microRNAs and proteins as well as regulating transcription and splicing. Moreover, most circRNAs are aberrantly expressed in different cancer types, and some of them have been reported to play important roles in the development and progression of cancer. Given the lack of a 5′ cap structure and evidence of their ability to bind with ribosomes, circRNAs were generally considered as noncoding RNA. Notably, recent studies reported that endogenous circRNAs can be translated with a cap-independent manner, which redefines the functional roles of circRNA, further expanding the complexity of eukaryotic transcriptomes. This review aims to re-evaluate the functions and roles of circRNA from the cancer perspective. It discusses the current understanding of circRNA functions, the emerging roles of circRNA in cancer, and the challenges of future studies.