Circular RNAs in programmed cell death: Regulation mechanisms and potential clinical applications in cancer: A review

Circular RNAs (circRNAs) are a novel class of non-coding RNAs with covalently closed structures formed by reverse splicing of precursor mRNAs. The widespread expression of circRNAs across species has been revealed by high-throughput sequencing and bioinformatics approaches, indicating their unique properties and diverse functions including acting as microRNA sponges and interacting with RNA-binding proteins. Programmed cell death (PCD), encompassing various forms such as apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis, is an essential process for maintaining normal development and homeostasis in the human body by eliminating damaged, infected, and aging cells. Many studies have demonstrated that circRNAs play crucial roles in tumourigenesis and development by regulating PCD in tumor cells, showing that circRNAs have the potential to be biomarkers and therapeutic targets in cancer. This review aims to comprehensively summarize the intricate associations between circRNAs and diverse PCD pathways in tumor cells, which play crucial roles in cancer development. Additionally, this review provides a detailed overview of the underlying mechanisms by which circRNAs modulate various forms of PCD for the first time. The ultimate objective is to offer valuable insights into the potential clinical significance of developing novel strategies based on circRNAs and PCD for cancer diagnosis, prognosis, and treatment.