title: MicroRNA-200a inhibits CD133/1+ ovarian cancer stem cells migration and invasion by targeting E-cadherin repressor ZEB2.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Obstetrics and Gynaecology, Third Afﬁliated Hospital of Guangzhou Medical College, Guangzhou 510150, China.
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Wu
authors.forename: Rongjiao
authors.initials: R
authors.lastname: Guo
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.forename: Bing
authors.initials: B
authors.lastname: Zhou
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D001483:Base Sequence; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D020413:3' Untranslated Regions; D000071916:AC133 Antigen; D015703:Antigens, CD; D015820:Cadherins; D006023:Glycoproteins; D018398:Homeodomain Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C000606023:PROM1 protein, human; D010455:Peptides; D012333:RNA, Messenger; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2