The immunomodulatory roles of endogenous circular RNAs: Biogenesis, function, and therapeutic exploitation

Abstract

Circular RNAs (circRNAs), a unique class of noncoding RNAs characterized by the covalently closed circular structures, play multifaceted physiological roles through diverse molecular mechanisms, including acting as microRNA (miRNA) sponges/reservoirs, transcriptional regulators, protein scaffolds/recruiters, and templates for functional peptide translation. In this review, we delve into the spatiotemporal expression dynamics of circRNAs across infectious pathology (viral, bacterial, and fungal), dysregulated immune disorders, and tumor immunology, highlighting their potential roles as critical immunomodulators in maintaining immune homeostasis. Furthermore, we discuss innovative strategies to leverage circRNAs for clinical applications, including their potential as diagnostic biomarkers and engineered therapeutics to restore immune equilibrium in infectious, immune-related and oncological diseases.

Keywords: Autoimmune diseases; Circular RNA; Immune regulation; Infection; Inflammation; Tumor immunity.