title: Ectopic over-expression of miR-429 induces mesenchymal-to-epithelial transition (MET) and increased drug sensitivity in metastasizing ovarian cancer cells.
abstract: OBJECTIVE
  We recently determined that the ectopic over-expression of miR-429 and other members of the miR-200 family of microRNAs in ovarian cancer (OC) mesenchymal-like cell lines induces mesenchymal-to-epithelial transition (MET) with a concomitant increase in sensitivity to platinum drugs. We sought to determine if metastasizing OC cells isolated from an OC patient could also be induced by miR-429 to undergo MET and become sensitized to established first-line platinum-based therapies.
  
  
  METHODS
  We established and characterized a new primary cell line (OCI-984) from free-floating OC cells isolated from the ascites fluid of an advanced stage OC patient. miR-429 was ectopically over-expressed in these cells.
  
  
  RESULTS
  The over-expression of miR-429 in OCI-984 cells induced morphological, functional and molecular changes consistent with MET and a concomitant significant increase in the sensitivity of the converted cells to cisplatin.
  
  
  CONCLUSIONS
  Our findings indicate that the miR-200 family of microRNAs, and miR-429 in particular, play a critical role in the functioning of OC metastasizing cells and that targeted delivery of miR-429, and perhaps other miR-200 family members, in combination with platinum-based chemotherapies may be an effective strategy in reducing OC metastasis and tumor recurrence.
authors.affiliation: Integrated Cancer Research Center, School of Biology and Parker H. Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Drive, Atlanta GA 30332, USA. Electronic address: Lijuan.Wang@biology.gatech.edu.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Integrated Cancer Research Center, School of Biology and Parker H. Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Drive, Atlanta GA 30332, USA. Electronic address: rmezencev3@gatech.edu.
authors.forename: Roman
authors.initials: R
authors.lastname: Mezencev
authors.affiliation: Bioptická Laboratoř, s.r.o., Pilsen, Czech Republic; Department of Pathology, Louis Pasteur University Hospital, Kosice, Slovakia. Electronic address: svajdler@yahoo.com.
authors.forename: Marián
authors.initials: M
authors.lastname: Švajdler
authors.affiliation: Ovarian Cancer Institute, 960 Johnson Ferry Road, Suite 130 Atlanta, GA 30342, USA. Electronic address: benedict.benigno@ugynonc.com.
authors.forename: Benedict B
authors.initials: BB
authors.lastname: Benigno
authors.affiliation: Integrated Cancer Research Center, School of Biology and Parker H. Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Drive, Atlanta GA 30332, USA; Ovarian Cancer Institute, 960 Johnson Ferry Road, Suite 130 Atlanta, GA 30342, USA. Electronic address: john.mcdonald@biology.gatech.edu.
authors.forename: John F
authors.initials: JF
authors.lastname: McDonald
mesh_terms: D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C546363:MIRN429 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin
keywords: EMT; MET; Metastasis; MicroRNAs; Ovarian cancer