Background:Chemotherapy resistance is a significant cause for poor prognosis of epithelial ovarian cancer (EOC). However, the molecular mechanism of chemo-resistance remains unclear, and developing available therapies and effective biomarkers for resistant EOC is in urgent demand. Stemness of cancer cells directly results in chemo-resistance. Exosomal miRNAs rebuild tumor microenvironment (TME) and act as widely used clinical liquid biopsy markers.Methods:In our study, high throughput screenings and comprehensive analysis were performed to screen for miRNAs, which were both up-regulated in resistant EOC tissues and related to stemness, and miR-6836 was identified accordingly.Results:Clinically, high miR-6836 expression was closely correlated with poor chemotherapy response and survival for EOC patients. Functionally, miR-6836 promoted EOC cell cisplatin resistance by increasing stemness and suppressing apoptosis. Mechanistically, miR-6836 directly targeted DLG2 to enhance Yap1 nuclear translocation, and was regulated by TEAD1 forming the positive feedback loop: miR-6836-DLG2-Yap1-TEAD1. Furthermore, miR-6836 could be packaged into secreted exosomes in cisplatin-resistant EOC cells and exosomal miR-6836 was able to be delivered into cisplatin-sensitive EOC cells and reverse their cisplatin response.Conclusion:Our study revealed the molecular mechanisms of chemotherapy resistance, and identified miR-6836 as the possible therapeutic target and effective biopsy marker for resistant EOC.