MicroRNA-124 Controls Transforming Growth Factor β1-Induced Epithelial-Mesenchymal Transition in the Retinal Pigment Epithelium by Targeting RHOG

Invest Ophthalmol Vis Sci. 2016 Jan 1;57(1):12-22. doi: 10.1167/iovs.15-17111.


Purpose: MicroRNA-124 (miR-124) is thought to be involved in the epithelial-mesenchymal transition (EMT) of RPE. We investigated the regulation of TGF-β1-induced EMT by miR-124 in human RPE cells (ARPE-19).

Methods: Expression of miR-124 was evaluated after TGF-β1 treatment by quantitative RT-PCR. Phenotypic alterations were analyzed by Western blot analysis and immunocytochemical staining. Target validation was performed by a luciferase reporter assay to identify the putative target of miR-124.

Results: The expression level of miR-124 was downregulated during the progression of EMT. Overexpression of miR-124 upregulated the levels of zonular occludens 1 and occludin, and downregulated those of fibronectin, α-smooth muscle actin, and vimentin. Furthermore, inhibition of endogenous miR-124 increased and decreased the levels of mesenchymal and epithelial factors, respectively. TargetScan predicted two well-conserved and two vertebrate-only conserved miR-124 target sequences in the 3' untranslated region (UTR) of the Ras homology Growth-related (RHOG) mRNA. Direct targeting of this 3' UTR by miR-124 was demonstrated using a luciferase assay. Silencing of RHOG using a specific siRNA had identical effects on EMT regulation. Overexpression of miR-124 repressed TGF-β1-induced RPE cell-collagen gel lattice contraction by altering cell spreading/cell-to-cell adhesion.

Conclusions: This study describes the regulation of EMT in RPE cells by TGF-β1/miR-124/RHOG signaling and suggests that the supplement of miR-124 exogenously would be a valuable therapeutic approach for the prevention or treatment of proliferative vitreoretinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Far-Western
  • Blotting, Western
  • Cell Line
  • Epithelial-Mesenchymal Transition / drug effects*
  • Gene Expression Regulation*
  • Humans
  • Immunohistochemistry
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Retinal Pigment Epithelium / metabolism*
  • Retinal Pigment Epithelium / pathology
  • Transforming Growth Factor beta1 / therapeutic use*
  • Vitreoretinopathy, Proliferative / drug therapy
  • Vitreoretinopathy, Proliferative / genetics*
  • Vitreoretinopathy, Proliferative / metabolism
  • rho GTP-Binding Proteins / biosynthesis
  • rho GTP-Binding Proteins / genetics*


  • MIRN124 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • RHOG protein, human
  • rho GTP-Binding Proteins