title: MicroRNA-200c overexpression plays an inhibitory role in human pancreatic cancer stem cells by regulating epithelial-mesenchymal transition.
abstract: OBJECTIVE
  Cancer stem cells (CSCs) are believed to be the 'seed cell' in cancer recurrence and metastasis. MicroRNAs (miRNAs) have emerged as potential therapeutic candidates due to their ability to regulate the epithelial-mesenchymal transition (EMT). The goal of this study was to investigate the effect of miRNA-200c (miR-200c) on the EMT, tumorigenesis, colony formation, invasion and chemoresistance of human pancreatic cancer stem cells (PCSCs).
  
  
  METHODS
  PCSCs with CD24+CD44+ESA+ as the marker was sorted from PANC-1 cell line by fluorescence activated cell sorter (FACS). Quantitative real-time PCR (qRT-PCR) assay was used to detect the relative mRNA expression levels of miR-200c and EMT-associated phenotypes. Transfection of miR-200c mimic into PCSCs was performed to establish miR- 200c overexpressed cells. The assays of colony forming, cellular invasion and survival in vitro and tumor progression in vivo were performed.
  
  
  RESULTS
  Expression of miR-200c was significantly reduced in PCSCs compared with PANC-1 cells. However, the stable over expression of the miR-200c in the PCSCs resulted in a significant down-regulation of zinc-finger E-box binding homeobox 1 (ZEB1) and the Vimentin expression, an upregulation of the E-cadherin expression as well as a decrease of colony forming, chemoresistance and invasion in vitro and xenograft growth in vivo in nude mice by inhibition of the EMT.
  
  
  CONCLUSIONS
  Our study demonstrated that miR-200c may become a new therapeutic target for gene therapy in patients suffered from pancreatic cancer.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, The Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, China - hbht68@163.com.
authors.forename: C
authors.initials: C
authors.lastname: Ma
authors.forename: Y C
authors.initials: YC
authors.lastname: Ding
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Meng
authors.forename: T
authors.initials: T
authors.lastname: Huang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D015820:Cadherins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D014162:Transfection / Q000379:methods; D014746:Vimentin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D014746:Vimentin