Objective: To investigate the role of microRNA-486-5p (miR-486-5p) in nonsmall-cell lung cancer (NSCLC) resistance to cisplatin.
Methods: This retrospective study examined tumours and normal lung tissues from patients with NSCLC. The levels of miR-486-5p in NSCLC and normal tissues were determined using reverse transcription–polymerase chain reaction. The binding site of miR-486-5p on twinfilin actin binding protein 1 (TWF1) mRNA was predicted using TargetScan and investigated using a luciferase reporter gene assay. Cytotoxicity assays were used to measure the sensitivity of A549 cells to cisplatin. Western blotting was used to measure the levels of specific proteins. The role of miR-486-5p in the resistance of A549 to cisplatin was verified in vivo using a nude mouse tumorigenicity assay.
Results: MiR-486-5p levels were downregulated in NSCLC tissues compared with normal lung tissues. Lower levels of miR-486-5p were associated with reduced overall survival of patients with NSCLC. The cisplatin-resistant NSCLC cell line, A549/DDP, had lower miR-486-5p levels compared with A549 cells. Luciferase reporter gene assays confirmed that miR-486-5p bound to the 3ʹ untranslated region of TWF1 mRNA. In vivo experiments demonstrated the inhibitory effect of miR-486-5p on chemotherapy resistance.
Conclusion: MiR-486-5p appears to play an important role in improving chemotherapy sensitivity to cisplatin.
Keywords: MicroRNA-486-5p; cisplatin resistance; epithelial–mesenchymal transition; nonsmall-cell lung cancer; twinfilin actin binding protein 1.