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

Abstract

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 miR-200a 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.