DDP Induced Cytotoxicity through miR-215-5p/COL5A1/FSTL1 Axis to Regulate Autophagy in Lung Adenocarcinoma Cells.

ABSTRACT

BACKGROUND: Cisplatin (DDP) resistance remains a major challenge in the treatment of lung adenocarcinoma (LUAD). Autophagy is an important mechanism to generate drug resistance. It has been established that COL5A1 has been shown to accelerate LUAD metastasis and affect cellular processes. METHODS: We investigated the role of COL5A1 in DDP resistance using the H1299/DDP and A549/DDP cell lines. Flow cytometry, CCK8, and western blot assays were used to detect apoptosis, cell viability, and autophagy. In addition, upstream miRNAs were screened using bioinformatics methods. MS2-RIP assay and luciferase reporter gene assay were used to validate miRNA interaction with COL5A1. Transfection experiments and western blot experiments were performed to investigate miRNA targeting to COL5A1 and its regulation of autophagy through FSTL1. The role of miRNA and COL5A1 in LUAD cisplatin resistance was also verified in vivo. RESULTS: The down-regulation of COL5A1 significantly reduced the survival and autophagy of DDP-resistant cells while enhancing apoptosis. MiR-215-5p was found to be a direct regulator of COL5A1, which affects autophagy through FSTL1. CONCLUSION: The present study demonstrated that miR-215-5p regulated COL5A1 to modulate FSTL1 and autophagy, thereby attenuating LUAD resistance to DDP. These findings deepen the understanding of LUAD pathogenesis and provide potential insights into therapeutic strategies.