Hypoxia-Induced microRNAs confer survival advantage in bladder cancer by fine-tuning oncogenic Pathways

INTRODUCTION: Bladder cancer (BC) is influenced by hypoxic conditions, which promote tumor progression and resistance to therapy. MicroRNAs (miRNAs) play key roles in regulating gene expression under hypoxia. METHODS: This study utilized a miRNA array to compare expression profiles under normoxic and hypoxic conditions. We analyzed 1024 genes, focusing on differentially expressed miRNAs. Survival analysis was performed using a cohort of 408 BC patients from TCGA (The Cancer Genome Atlas). Target prediction for hypoxia-inducible factors (HIFs) and cancer-related genes was performed. RESULTS: Of 1024 miRNAs, 508 were downregulated and 516 upregulated in hypoxia. Four miRNAs (hsa-miR-210, hsa-miR-4435, hsa-miR-6875, hsa-miR-193b) were upregulated >50-fold, and four (hsa-miR-1250, hsa-miR-1288, hsa-miR-362, hsa-miR-6828) were downregulated. Upregulated miRNAs were associated with a trend toward improved overall survival in 408 BC patients (Log-rank p = 0.049). Three downregulated miRNAs targeted HIF-1α, while three upregulated miRNAs targeted HIF-3α. Hsa-miR-210 targeted AGO2 and USP10, with hsa-miR-4435 also targeting AGO2. CONCLUSION: BC under hypoxia exhibits a specific miRNA profile targeting HIFs and cancer-related genes including AGO2 and USP10, potentially influencing treatment success and survival.