Epigenetic modulation of cisplatin sensitivity by the M6A-linked ceRNA network in non-small cell lung cancer

Cisplatin resistance significantly impedes effective treatment of non-small cell lung cancer (NSCLC). This study investigates the role of the N6-methyladenosine (M6A)-related circFUT8/miR-185-5p/HNRNPC competing endogenous RNA (ceRNA) axis in NSCLC cisplatin resistance. Bioinformatics analysis identified HNRNPC, a critical M6A modification-related gene, as a promoter of NSCLC proliferation and metastasis. Our in vitro and in vivo experiments reveal that circFUT8 upregulates HNRNPC by sponging miR-185-5p, thus enhancing NSCLC cell proliferation, migration, and invasion while reducing apoptosis and sensitivity to cisplatin. These findings highlight the circFUT8/miR-185-5p/HNRNPC axis as a potential target to overcome chemoresistance in NSCLC.NEW & NOTEWORTHY This study identifies the N6-methyladenosine (M6A)-linked circFUT8/miR-185-5p/HNRNPC competing endogenous RNA (ceRNA) network as a key regulator of cisplatin resistance in non-small cell lung cancer (NSCLC). By revealing how circFUT8 modulates HNRNPC through miR-185-5p, this work provides insights into the molecular mechanisms of chemoresistance. The findings suggest potential therapeutic strategies targeting the circFUT8/miR-185-5p/HNRNPC axis to overcome cisplatin resistance in NSCLC, opening new avenues for improved treatment outcomes.