Deregulation of let-7e in epithelial ovarian cancer promotes the development of resistance to cisplatin

摘要: Drug resistance remains a major clinical obstacle to successful treatment in ovarian cancer patients, and the evidence of microRNAs involvement drug has been emerging recently. In this report, we investigated role let-7e development cisplatin-resistant cancer. On cellular level, expression was significantly reduced human epithelial (EOC) cell line A2780/CP compared with parental A2780 decreased concentration-dependent manner A2780, SKOV3 ES2 cells treated cisplatin. Overexpression by transfection agomir could resensitize reduce cisplatin-resistant-related proteins enhancer zeste 2 (EZH2) cyclin D1 (CCND1), whereas inhibitors increased cisplatin cells. Quantitative methylation-specific PCR analysis showed hypermethylation CpG island adjacent cells, demethylation 5-aza-CdR or pYr-let-7e-shRNA plasmid containing unmethylated DNA sequence restore partly chemoresistance. addition, combined agomirs inhibited growth xenograft more effectively than alone. Diminished EZH2 CCND1 higher concentrations tumor tissue mice subjected administration addition were revealed immunohistochemistry atomic absorption spectroscopy, respectively. Taken together, our findings suggest that may act as promising therapeutic target for improvement sensibility EOC.