Downregulation of miR-429 contributes to the development of drug resistance in epithelial ovarian cancer by targeting ZEB1.

Drug resistance is an obstacle to the treatment of epithelial ovarian cancer. Recently, research has suggested that miRNAs (microRNAs) are involved in cancer development, and speculation has been made about their possible involvement in drug resistance. Thus, we attempted to identify selected miRNAs involved in the development of chemo-resistance in epithelial ovarian cancer. Using miRNA profiles of a panel of cisplatin-resistant (SKOV3/DDP) cells, we validated data using quantitative real time-PCR (QRT-PCR), and studied the effects of miR-429 on cancer cell chemo-sensitivity, using gain- and loss-of-function studies. Data show that SKOV3/DDP expressed less miR-429 compared with parental SKOV3 cells and lower miR-429 expression conferred shorter overall survival (OS) and less progression-free survival (PFS) than the patients with more miR-429 expression (P < 0.01). Upregulation of miR-429 increases cisplatin sensitivity in epithelial ovarian cancer cells. Studies have confirmed that the zinc finger E-box binding homeobox1 (ZEB1) is a direct and functional target of miR-429 and that over-expression of miR-429 reduces autophagy-related protein anti-ATG7, anti-LC3A/B (P < 0.05). Thus, overexpression of miR-429 may suppress ZEB1, and may be a potential sensitizer to cisplatin treatment that may have therapeutic implications.