Crosstalk between microRNA and oxidative stress in ovarian cancer: diagnosis, pathogenesis and therapeutic resistance

Abstract

Ovarian cancer (OC) is the most lethal gynecologic malignancy due to late-stage diagnosis, frequent recurrence, and resistance to therapy. Emerging evidence highlights oxidative stress (OS)-a redox imbalance caused by excessive reactive oxygen species (ROS)-as a key contributor to tumor development and therapy failure. This article presents a narrative review of the bidirectional relationship between oxidative stress and microRNAs (miRNAs) in OC, emphasizing their molecular crosstalk, clinical relevance, and therapeutic potential. A targeted synthesis of recent experimental and clinical studies was conducted to explore how redox biology and miRNA dysregulation contribute to OC pathogenesis and treatment resistance. ROS promotes genomic instability, epithelial-mesenchymal transition (EMT), angiogenesis, immune evasion, and chemoresistance. Redox-responsive miRNAs (e.g., miR-29b, miR-200a/c, miR-145-5p, miR-484, miR-21) regulate antioxidant defenses, DNA repair, apoptosis. OS modulates miRNA biogenesis via transcriptional and epigenetic changes, and miRNAs form feedback loops that influence ROS levels and tumor progression. Circulating and exosomal miRNAs show promise as non-invasive biomarkers, but require further clinical validation. Therapeutic approaches targeting the ROS-miRNA axis-including mimics, antagomiRs, and nanocarriers-show preclinical potential, though challenges in delivery and toxicity remain. The dynamic OS-miRNA interplay represents a novel regulatory axis in OC. Exploiting this axis may enhance early diagnosis and therapy. Future work should integrate redox profiling with miRNA expression to personalize treatment and assess performance relative to existing modalities like PARP inhibitors.