MicroRNA-200a inhibits CD133/1+ovarian cancer stem cells migration and invasion by targeting E-cadherin repressor ZEB2

Objectives. MicroRNA-200a (miR-200a) has been reported to be a prognostic marker and to play an important role in ovarian cancer progression. The aim of the study was to elucidate the mechanism of miR200a involved in migration and invasion in CD133/1+ ovarian cancer stem cells (OCSCs). Methods. The expression of miR-200a between CD133/1+ and CD133/1- cells was performed using real-time PCR, and wound healing assay and matrigel invasion assay were used to detect migration and invasion of CD133/1+ cells, respectively, target gene regulated by miR-200a was detected using Dual Luciferase Reporter system, The expression levels of target gene were confirmed using real-time PCR and western blot. Results. miR-200a was downregulated in CD133/1+ cells compared with CD133/1- cells, and overexpression of miR-200a significantly reduced CD133/1+ cells migration and invasion compare with negative control (NC) (p<0.05). The 3'-UTR of ZEB2 mRNA, a transcriptional repressor of E-cadherin, was found to be regulated directly by miR-200a. In addition, when miR-200a was overexpressed in CD133/1+ cells, the mRNA and protein levels of ZEB2 were both suppressed, which resulted in an increase in the E-cadherin expression level, suggesting that ZEB2 was a functionally important target of miR-200a in CD133/1+ cells. Conclusions. Our results suggest that loss of expression of miR-200a may play a critical role in the repression of E-cadherin by ZEB2, thereby enhancing migration and invasion in CD133/1+ cells. (C) 2011 Elsevier Inc. All rights reserved.