Circular RNA-mediated regulation of key signaling pathways in cardiovascular diseases: a review

Cardiovascular diseases (CVDs) are globally prevalent pathologies driven by dysregulated signaling networks. Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs produced by back-splicing mechanism, in which a downstream 5′ splice site joins an upstream 3′ splice site, have emerged as critical regulators of CVD pathogenesis. This review examines their lifecycle, including biogenesis, nuclear export mechanisms, subcellular localization, and degradation, along with their functional roles in microRNA sequestration, protein interactions, transcriptional regulation, and polypeptide translation. Recent advances in circRNA engineering are also discussed, including in vitro synthesis strategies, delivery platforms, vaccine development, gene editing, and aptamers (synthetic high-affinity nucleic acid ligands). Furthermore, we explore the latest findings that focus on how circRNAs modulate these core CVD-related pathways. The unique expression patterns and engineering potential of circRNAs render them valuable candidates for biomarker and therapy development. This review connects the fundamental biology of circRNAs to recent technological advances, offering a roadmap for leveraging the functional interaction between circRNAs and signaling pathways in CVD precision medicine.