title: The expression of microRNA-451 in human endometriotic lesions is inversely related to that of macrophage migration inhibitory factor (MIF) and regulates MIF expression and modulation of epithelial cell survival.
abstract: OBJECTIVE
  What is the role of microRNA-451 (miR-451) in human endometriotic tissue?
  
  
  CONCLUSIONS
  miR451 expression was elevated in endometriotic lesion tissue. MiR451 modulated the expression of macrophage migration inhibitory factor and limited cell survival.
  
  
  BACKGROUND
  microRNAs are post-transcriptional regulators of gene expression which have been reported to be mis-expressed in endometriotic tissue. The exact pattern of expression and role of miR451 in endometriosis is currently unknown.
  
  
  METHODS
  Thirty women with endometriosis are included in the study.
  
  
  METHODS
  Matched eutopic (N = 30) and endometriotic lesion tissue (N = 43) were collected. miR-451, macrophage migration inhibitory factor (MIF), cyclin E1 (CCNE) and phosphatase and tensin homolog (PTEN) mRNA expression were examined by quantitative real-time (qRT)-PCR while MIF protein expression was evaluated by western blot analysis. miR-451 regulation of MIF in vitro translation was confirmed by 3'untranslated region (UTR) reporter assays and western blot analysis. The effect of miR-451 on cell survival was assessed using a human endometrial epithelial cell line (HES).
  
  
  RESULTS
  Compared with eutopic endometrium, both MIF mRNA and protein were significantly (P < 0.05) decreased in endometriotic lesions and this was associated with a significant (P < 0.05) increase in miR-451 expression. Transfection of HES cells with luciferase reporter constructs for MIF revealed that miR-451 specifically bound to the 3'UTR to regulate expression. Further, forced expression of miR-451 induced a significant (P < 0.05) down-regulation of both MIF mRNA and protein in HES cells which was associated with a significant (P < 0.05) reduction in cell survival. Inhibition of MIF using a specific antagonist verified that reduction of MIF contributes to HES cell survival.
  
  
  CONCLUSIONS
  miR-451 and MIF expression were only examined in tissue from women with endometriosis.
  
  
  CONCLUSIONS
  Our data support the hypothesis that miR-451 is elevated in endometriotic tissue and, through regulating MIF expression, may function to limit endometriotic lesion cell survival.
  
  
  BACKGROUND
  This study was funded by the National Institutes of Health/NICHD by grant NIH HD069043 to W.B.N. The authors have no competing interests.
authors: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA Institute for Reproductive Health and Regenerative Medicine, Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors: Amanda
authors: A
authors: Graham
authors: Department of Department of Obstetrics, Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors: Tommaso
authors: T
authors: Falcone
authors: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA Institute for Reproductive Health and Regenerative Medicine, Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA wnothnic@kumc.edu.
authors: Warren B
authors: WB
authors: Nothnick
mesh_terms: D000328:Adult; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; C531201:MIRN451 microRNA, human; D008263:Macrophage Migration-Inhibitory Factors; D035683:MicroRNAs; D015513:Oncogene Proteins; D012333:RNA, Messenger; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: endometriosis; macrophage migration inhibitory factor; miRNA
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