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

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Author(s)
Jong Hwa JunChoun-Ki Joo
Keimyung Author(s)
Jun, Jong Hwa
Department
Dept. of Ophthalmology (안과학)
Journal Title
Investigative Ophthalmology & Visual Science
Issued Date
2016
Volume
57
Issue
1
Keyword
Epithelial–mesenchymal transition (EMT)MicroRNA-124 (miR-124)Retinal pigment epithelium (RPE)Ras homology Growth-related (RHOG)Transforming growth factor beta (TGF-b)
Abstract
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.
Keimyung Author(s)(Kor)
전종화
Publisher
School of Medicine
Citation
Jong Hwa Jun and Choun-Ki Joo. (2016). MicroRNA-124 Controls Transforming Growth Factor β1-Induced Epithelial-Mesenchymal Transition in the Retinal Pigment Epithelium by Targeting RHOG. Investigative Ophthalmology & Visual Science, 57(1), 12–22. doi: 10.1167/iovs.15-17111
Type
Article
ISSN
0146-0404
DOI
10.1167/iovs.15-17111
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33239
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Ophthalmology (안과학)
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