Coding circular RNA in human cancer

circular RNA (circRNA) is a covalently closed single-stranded RNA that lacks 5’ and 3’ ends and has long been considered a noncoding RNA. With the development of high-throughput sequencing and bioinformatics technology, the understanding of circRNA has become increasingly advanced. Recent studies have shown that some cytoplasmic circRNAs can be effectively translated into detectable proteins, further indicating the importance of circRNA in cellular pathology and physiological functions. Internal ribosome entry site (IRES) and N⁶-methyladenosine (m⁶A) mediated cap-independent translation initiation are considered potential mechanisms of circRNA translation. Multiple circRNAs have been shown to play crucial roles in human cancer. This paper provides an overview of the nature and functions of circRNA and describes the possible mechanisms underlying the initiation of circRNA translation. We summarized the emerging functions of circRNA-encoded proteins in human cancer. Finally, we discuss the therapeutic potential of circRNAs and the challenges of research in this field. This review on circRNA translation will reveal a hidden human proteome and enhance our understanding of the importance of circRNAs in human malignant tumors.