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 an miRNA array to compare expression profiles under normoxic and hypoxic conditions. We analyzed 1,024 miRNAs, 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 1,024 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.