Objective: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Despite significant advancements in immunotherapy and targeted therapy, chemotherapy remains the cornerstone of treatment for advanced NSCLC patients. Cisplatin, a widely used chemotherapeutic agent, exerts its effects by inducing apoptosis through DNA interaction. However, most patients eventually develop resistance to cisplatin. MicroRNA (miRNA)-based therapies have shown great potential in overcoming cisplatin resistance. While miR-150-3p has demonstrated tumor-suppressive effects in various cancers, its impact on cisplatin sensitivity in NSCLC remains unclear.

Materials and Methods: Microarray analysis was performed to detect miRNA expression changes in NSCLC cells following cisplatin treatment. The prognostic value of miR-150-3p and its differential expression between normal and tumor tissues were analyzed using The Cancer Genome Atlas (TCGA) database. The effects of miR-150-3p overexpression in A549 and H358 cells were validated using CCK8 assay, colony formation assay, wound healing scratch assay, and transwell migration assay. Luciferase reporter assay was conducted to identify the target genes of miR-150-3p.

Results: MiR-150-3p was significantly upregulated in NSCLC cells after cisplatin treatment, and its high expression was associated with improved prognosis in NSCLC patients. Overexpression of miR-150-3p suppressed cell proliferation, colony formation, wound healing capacity, and migration in A549 and H358 cells. Exogenous miR-150-3p enhanced the anti-proliferative and anti-migratory effects of cisplatin. MiR-150-3p overexpression downregulated AKT2 expression. Luciferase reporter assays confirmed that miR-150-3p directly binds to the 3' untranslated region (3'UTR) of AKT2.

Conclusions: This study reveals that miR-150-3p enhances cisplatin efficacy in NSCLC cells by targeting AKT2.