Circular RNAs as molecular bridges: dual regulation of ferroptosis and immunity in cancer

Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules generated by back-splicing events of precursor mRNAs, characterized by superior structural stability, strict tissue specificity, and diverse regulatory functions. Ferroptosis is an iron-dependent, lipid peroxidation-driven regulated cell death (RCD) distinct from classical apoptosis and necrosis; remodeling of the tumor immune microenvironment (TIME) directly modulates cancer progression and therapeutic efficacy. Both are core targets in cancer biology and translational oncology. Emerging evidence shows circRNAs act as "molecular bridges" to simultaneously regulate ferroptosis and anti-tumor immunity via miRNA sponging, protein interaction/scaffolding, and de novo encoding of functional peptides. This review systematically elaborates the molecular mechanisms of circRNA-mediated ferroptosis-immunity crosstalk in cancer, where ferroptosis and anti-tumor immunity reciprocally regulate each other through inflammatory signals and immune effectors. CircRNAs act as "molecular bridges" by simultaneously targeting key nodes in both pathways via a single regulatory event, a concept defined here as "dual regulation". we focused on three major regulatory modalities, and explores their potential as non-invasive diagnostic biomarkers and novel therapeutic targets, providing new perspectives for precision cancer therapy via dual targeting of ferroptosis and immune pathways.