The hsa-miR-520a/MYO19 Axis Modulates Tumor Progression and Immune Evasion Through Ferroptosis in Lung Squamous Cell Carcinoma: Insights from Pan-Cancer Analysis

Background Lung squamous cell carcinoma (LUSC) is a highly aggressive malignancy with limited therapeutic options and poor clinical outcomes. Recent studies have underscored the critical role of ferroptosis—a regulated form of cell death—in tumor development, immune regulation, and resistance to therapy. MYO19, a mitochondrial trafficking protein, has been implicated in cancer progression; however, the regulatory relationship between MYO19 and hsa-miR-520a, as well as their combined influence on tumor progression, immune modulation, and ferroptosis resistance in LUSC, remains largely unexplored. Methods Pan-cancer analyses, bioinformatics, and experimental validation were used to investigate MYO19 and hsa-miR-520a expression, interaction, and function in LUSC. Survival analyses, miRNA mimic/inhibitor treatments, and assays for proliferation, migration, and ferroptosis sensitivity were performed. Results MYO19 was significantly overexpressed in LUSC and was associated with poor prognosis, advanced tumor stages, decreased immune cell infiltration, and increased resistance to ferroptosis. In contrast, hsa-miR-520a, a tumor-suppressive microRNA, was markedly downregulated and exhibited a strong inverse correlation with MYO19 expression. Kaplan-Meier survival analysis revealed that patients with high hsa-miR-520a expression or low MYO19 expression had significantly improved overall survival. Functional assays confirmed that hsa-miR-520a directly targets MYO19, leading to suppressed cell proliferation and migration, while enhancing sensitivity to ferroptosis through regulation of ferroptosis-associated genes such as GPX4. Furthermore, hsa-miR-520a promoted immune cell infiltration, highlighting its potential role in counteracting immune evasion. Conclusion The hsa-miR-520a/MYO19 axis is a key regulator of tumor progression, immune evasion, and ferroptosis resistance in LUSC, offering new insights into disease mechanisms and potential therapeutic targets.