title: Targeting of syndecan-1 by micro-ribonucleic acid miR-10b modulates invasiveness of endometriotic cells via dysregulation of the proteolytic milieu and interleukin-6 secretion.
abstract: OBJECTIVE
  To study the function of syndecan-1 (SDC1) and its potential regulator miR-10b in endometriosis.
  
  
  METHODS
  Experimental laboratory study.
  
  
  METHODS
  University medical center.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  The human endometriotic cell line 12Z was transiently transfected with SDC1 small interfering RNA or miR-10b precursors and investigated for changes in cell behavior and gene expression. 12Z and primary eutopic endometrial stroma cells of two American Society for Reproductive Medicine class III endometriosis patients were transfected with miR-10b precursors to investigate posttranscriptional regulation of SDC1.
  
  
  METHODS
  Quantitative polymerase chain reaction, Western blotting, flow cytometry, 3' untranslated region luciferase assays, and zymography were used to measure miR-10b-dependent targeting of SDC1 and SDC1-dependent expression changes of proteases and interleukin-6. Altered cell behavior was monitored by Matrigel invasion assays, cell viability assays, and mitogen-activated protein kinase activation blots.
  
  
  RESULTS
  Knockdown of SDC1 inhibited Matrigel invasiveness by >60% but did not affect cell viability. Interleukin-6 secretion, matrix metalloproteinase-9 expression, and matrix metalloproteinase-2 activity were reduced, whereas plasminogen activator inhibitor-1 protein expression was up-regulated. miR-10b overexpression significantly down-regulated SDC1, reduced Matrigel invasiveness by 20% and cell viability by 14%, and decreased mitogen-activated protein kinase activation in response to hepatocyte growth factor.
  
  
  CONCLUSIONS
  Syndecan-1, a target of miR-10b, inhibits epithelial endometriotic cell invasiveness through down-regulation of metalloproteinase activity and interleukin-6.
authors.affiliation: Department of Gynecology and Obstetrics, Münster University Hospital, Münster, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schneider
authors.forename: Nadja
authors.initials: N
authors.lastname: Kässens
authors.forename: Burkhard
authors.initials: B
authors.lastname: Greve
authors.forename: Hebatallah
authors.initials: H
authors.lastname: Hassan
authors.forename: Andreas N
authors.initials: AN
authors.lastname: Schüring
authors.forename: Anna
authors.initials: A
authors.lastname: Starzinski-Powitz
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kiesel
authors.forename: Daniela G
authors.initials: DG
authors.lastname: Seidler
authors.forename: Martin
authors.initials: M
authors.lastname: Götte
mesh_terms: D001672:Biocompatible Materials; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D003094:Collagen; D004338:Drug Combinations; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000166:cytology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007797:Laminin; D020935:MAP Kinase Signaling System / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans; D034741:RNA, Small Interfering / Q000235:genetics; D053668:Syndecan-1 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D004338:Drug Combinations; C508600:IL6 protein, human; D015850:Interleukin-6; D007797:Laminin; C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D017395:Plasminogen Activator Inhibitor 1; D011509:Proteoglycans; D034741:RNA, Small Interfering; C508241:SDC1 protein, human; C051321:SERPINE1 protein, human; D053668:Syndecan-1; C059485:matrigel; D003094:Collagen; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9