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Life sciences · Journal article
Discover Oncology · October 21, 2026
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Circular RNAs (circRNAs), once regarded as aberrant splicing by‑products, have emerged as pivotal non‑coding regulators in lung cancer. This review systematically summarizes the biogenesis, molecular modes of action, biological functions, therapeutic‑resistance‑related roles, and translational prospects of circRNAs in lung malignancy. CircRNAs are generated through back‑splicing modulated by cis‑acting genomic elements and trans‑acting RNA‑binding proteins. Benefiting from their covalently closed circular conformation, circRNAs exhibit extraordinary resistance to exonuclease degradation and exert versatile biological effects via multiple mechanisms: acting as microRNA sponges, scaffolding or decoying RNA‑binding proteins, mediating nuclear transcriptional and epigenetic regulation, and even translating bioactive peptides through cap‑independent pathways. Dysregulated circRNAs drive core oncogenic hallmarks in lung cancer, including uncontrolled proliferation, apoptosis escape, epithelial‑mesenchymal transition and metastasis, metabolic reprogramming, as well as tumour microenvironment remodelling and immune evasion. Furthermore, circRNAs participate in conferring resistance to chemotherapy, targeted tyrosine kinase inhibitor therapy, and immune checkpoint blockade. Owing to their high stability and detectability in diverse body fluids, circRNAs hold great promise as non‑invasive liquid‑biopsy biomarkers for early diagnosis, prognostic stratification and recurrence surveillance. Therapeutically, oncogenic circRNAs can be silenced by RNA interference, while synthetic tumour‑suppressive circRNAs can be delivered by lipid nanoparticles or engineered exosomes for intervention. Nevertheless, several bottlenecks remain for clinical implementation, such as inconsistent detection standards, context‑dependent dual functions, unsatisfactory in‑vivo delivery efficiency, and potential biosafety risks. Resolving these obstacles will accelerate the translation of circRNA‑oriented strategies toward clinical practice and provide novel opportunities for precision management of lung cancer.