Circ_IGF2BP1/miR-885-3p/TK1 axis regulates the malignant phenotype and chemotherapeutic resistance of lung adenocarcinoma cells via DNA damage and apoptosis

Chemotherapy resistance in lung adenocarcinoma (LUAD) limits clinical efficacy. In this study, we first established circ_IGF2BP1 knockdown models in LUAD cells (A549 and H1299). Using dual-luciferase reporter assays, functional analyses, and miR-885-3p rescue experiments, we demonstrated that circ_IGF2BP1 promotes LUAD cell proliferation, migration, and invasion by directly targeting miR-885-3p. Subsequent TargetScan database predictions identified thymidine kinase 1 (TK1) as a downstream target of miR-885-3p. Given the reported roles of miR-885-3p and TK1 in chemoresistance, we generated cisplatin-resistant LUAD cells (A549/DDP) and compared them with cisplatin-sensitive A549 controls. Overexpression or knockdown of circ_IGF2BP1 in these cell lines, combined with dual-luciferase reporter assays, Western blotting, functional studies, and miR-885-3p/TK1 rescue experiments, revealed that the circ_IGF2BP1/miR-885-3p/TK1 axis regulates malignant phenotypes and chemoresistance in both A549 and A549/DDP cells by modulating DNA damage and apoptosis. Furthermore, TK1 overexpression or knockdown in cisplatin-resistant cells confirmed its functional role in LUAD chemoresistance through cellular assays. In addition, qRT-PCR and clinical correlation analyses revealed that circ_IGF2BP1, miR-885-3p, and TK1 are closely associated with clinical diagnosis, prognosis, and treatment in LUAD patients. Collectively, these findings indicate that circ_IGF2BP1 modulates malignant phenotypes and cisplatin resistance in LUAD via the miR-885-3p/TK1 axis by regulating DNA damage and apoptosis pathways.