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

Fertil Steril. 2013 Mar 1;99(3):871-881.e1. doi: 10.1016/j.fertnstert.2012.10.051. Epub 2012 Nov 30.

Abstract

Objective: To study the function of syndecan-1 (SDC1) and its potential regulator miR-10b in endometriosis.

Design: Experimental laboratory study.

Setting: University medical center.

Patient(s): Not applicable.

Intervention(s): 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.

Main outcome measure(s): 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.

Result(s): 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.

Conclusion(s): Syndecan-1, a target of miR-10b, inhibits epithelial endometriotic cell invasiveness through down-regulation of metalloproteinase activity and interleukin-6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials
  • Cell Line
  • Cell Survival / physiology
  • Collagen
  • Drug Combinations
  • Endometriosis / genetics*
  • Endometriosis / metabolism
  • Endometriosis / pathology
  • Endometrium / cytology*
  • Female
  • Humans
  • Interleukin-6 / metabolism*
  • Laminin
  • MAP Kinase Signaling System / physiology
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • MicroRNAs / genetics*
  • Plasminogen Activator Inhibitor 1 / genetics
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Proteoglycans
  • RNA, Small Interfering / genetics
  • Syndecan-1 / genetics*
  • Syndecan-1 / metabolism
  • Transfection

Substances

  • Biocompatible Materials
  • Drug Combinations
  • IL6 protein, human
  • Interleukin-6
  • Laminin
  • MIRN10 microRNA, human
  • MicroRNAs
  • Plasminogen Activator Inhibitor 1
  • Proteoglycans
  • RNA, Small Interfering
  • SDC1 protein, human
  • SERPINE1 protein, human
  • Syndecan-1
  • matrigel
  • Collagen
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9