miR-98-5p contributes to cisplatin resistance in epithelial ovarian cancer by suppressing miR-152 biogenesis via targeting Dicer1

Epithelial ovarian cancer (EOC) is a highly lethal gynecological malignancy, and cisplatin resistance is usually correlated with the poor prognosis of EOC. Increasing evidence indicates that the dysregulation of miRNAs is related to chemotherapy sensitivity. In this study, we revealed that miR-98-5p, a member of the let-7 family, was enriched in cisplatin-resistant EOC cells compared with cisplatin-sensitive cells, and could promote cisplatin resistance in EOC cells. Further studies showed that miR-98-5p could directly target the 3'-UTR of Dicer1 and suppress its expression, causing global miRNA downregulation. By miRNA array and qRT-PCR verification, we identified miR-152 as the vital downstream target of the miR-98-5p/Dicer1 axis in EOC cells. Moreover, we demonstrated that the ectopic expression of miR-152 reversed cisplatin resistance both in vitro and in vivo by targeting RAD51, a central member in homologous recombination. Importantly, miR-98-5p expression, as determined by in situ hybridization in tumor tissues, was associated with poor outcome of EOC patients. Together, these findings suggest the essential role of the miR-98-5p/Dicer1/miR-152 pathway in regulating cisplatin resistance of EOC cells and provide a potential target for EOC therapy.