Circular RNAs in ferroptosis: regulation mechanism and potential clinical application in disease

Abstract

Ferroptosis, an iron-dependent non-apoptotic form of cell death, is reportedly involved in the pathogenesis of various diseases, particularly tumors, organ injury, and degenerative pathologies. Several signaling molecules and pathways have been found to be involved in the regulation of ferroptosis, including polyunsaturated fatty acid peroxidation, glutathione/glutathione peroxidase 4, the cysteine/glutamate antiporter system Xc-, ferroptosis suppressor protein 1/ubiquinone, and iron metabolism. An increasing amount of evidence suggests that circular RNAs (circRNAs), which have a stable circular structure, play important regulatory roles in the ferroptosis pathways that contribute to disease progression. Hence, ferroptosis-inhibiting and ferroptosis-stimulating circRNAs have potential as novel diagnostic markers or therapeutic targets for cancers, infarctions, organ injuries, and diabetes complications linked to ferroptosis. In this review, we summarize the roles that circRNAs play in the molecular mechanisms and regulatory networks of ferroptosis and their potential clinical applications in ferroptosis-related diseases. This review furthers our understanding of the roles of ferroptosis-related circRNAs and provides new perspectives on ferroptosis regulation and new directions for the diagnosis, treatment, and prognosis of ferroptosis-related diseases.