Inhibition of microRNA-214 promotes epithelial-mesenchymal transition process and induces interstitial cystitis in postmenopausal women by upregulating Mfn2

Exp Mol Med. 2017 Jul 21;49(7):e357. doi: 10.1038/emm.2017.98.

Abstract

Our study aims to investigate the roles that microRNA-214 (miR-214) plays in the epithelial mesenchymal transition (EMT) process and the development of interstitial cystitis (IC) in postmenopausal women by targeting Mitofusin 2 (Mfn2). IC bladder tissues and adjacent normal bladder tissues were collected from postmenopausal women. Immunohistochemistry (IHC) staining was conducted. The target relationship between miR-214 and Mfn2 was determined by a dual luciferase reporter gene assay. Adipose-derived mesenchymal stem cells (ADMSCs) were extracted from postmenopausal rats and assigned to the blank, mimics, miR-214 inhibitors, mimics negative control (NC), inhibitors NC, Mfn2 siRNA, miR-214 inhibitors and Mfn2 siRNA groups. Exosomes secreted by transfected ADMSCs were instilled into the bladders of postmenopausal rats. The expression of miR-214 and Mfn2 mRNA and EMT markers was assessed by qRT-PCR and western blotting. It was confirmed that Mfn2 was the target gene of miR-214 in IC. Compared with the normal bladder tissues, miR-214 decreased, but Mfn2 increased in IC bladder tissues. Compared with the blank group, the expression of miR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein increased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein decreased in the miR-214 mimics and Mfn2 groups. The expression of MiR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein decreased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein increased in the miR-214 inhibitors group. Our findings indicate that the inhibition of miR-214 promotes the EMT process and contributes to bladder wall fibrosis by up-regulating Mfn2, thus leading to the occurrence of IC in postmenopausal women.

Publication types

  • Retracted Publication

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Biomarkers / analysis
  • Cystitis, Interstitial / metabolism*
  • Cystitis, Interstitial / pathology
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition*
  • Exosomes / metabolism
  • Female
  • Fibrosis
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Humans
  • Mesenchymal Stem Cells / metabolism
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / physiology*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Postmenopause / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation
  • Urinary Bladder / pathology*

Substances

  • Biomarkers
  • MIRN214 microRNA, human
  • MicroRNAs
  • Mitochondrial Proteins
  • Nucleic Acid Synthesis Inhibitors
  • GTP Phosphohydrolases
  • MFN2 protein, human