Emerging functions of m6A-modified circRNAs and their targeting strategies in lung cancer

Lung cancer, especially non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related morbidity and mortality worldwide, largely due to challenges in early diagnosis, pronounced tumor heterogeneity, and frequent therapeutic resistance. N6-methyladenosine (m6A), the most prevalent RNA epigenetic modification, participates in tumorigenesis and progression by regulating various aspects of RNA metabolism. Circular RNAs (circRNAs), characterized by their covalently closed loop structure and high stability, have emerged as important regulators of tumor proliferation, metastasis, and drug resistance. Increasing evidence indicates that m6A modification influences circRNA biogenesis, stability, and translational potential, while circRNAs can reciprocally modulate the m6A machinery or act as molecular scaffolds within m6A regulatory networks. In this mini-review, we summarize recent advances regarding m6A-modified circRNAs in lung cancer, with particular emphasis on their roles in tumor growth and metastasis, ferroptosis, cancer stem cell maintenance, resistance to radiotherapy, chemotherapy, and targeted therapy, metabolic reprogramming, and the tumor immune microenvironment. Additionally, we discuss the diagnostic and therapeutic potential of m6A-circRNA interactions. Finally, we highlight the need for future studies to elucidate the dynamic regulation and clinical translation of the m6A–circRNA axis, aiming to provide novel strategies for precision therapy in lung cancer.