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Regulation of Long Noncoding RNA NEAT1/miR-320a/HIF-1α Competitive Endogenous RNA Regulatory Network in Diabetic Retinopathy
PURPOSE: To determine the mechanism that long noncoding RNA NEAT1 (lncNEAT1)/miR-320a competitive endogenous RNA (ceRNA) network regulates hypoxia-inducible factor–1α (HIF-1α) in ARPE-19 cells and its potential role in diabetic retinopathy (DR). METHODS: ARPE-19 cells were cultured in a normal or hi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10351022/ https://www.ncbi.nlm.nih.gov/pubmed/37432846 http://dx.doi.org/10.1167/iovs.64.10.11 |
Sumario: | PURPOSE: To determine the mechanism that long noncoding RNA NEAT1 (lncNEAT1)/miR-320a competitive endogenous RNA (ceRNA) network regulates hypoxia-inducible factor–1α (HIF-1α) in ARPE-19 cells and its potential role in diabetic retinopathy (DR). METHODS: ARPE-19 cells were cultured in a normal or high-glucose (HG) medium, and cell migration, invasion, and permeability were detected by scratch, transwell, and FITC-dextran staining assays. LncNEAT1, HIF-1α, ZO-1, occludin, N-cadherin, and vimentin levels were tested. The binding of lncNEAT1 to miR-320a was verified by dual-luciferase reporter assay, and the binding of miR-320a to HIF-1α by RIP assay. ARPE-19 cells were treated with lncNEAT1 or HIF-1α shRNA or miR-320a agomir to determine the activation of ANGPTL4/p-STAT3 pathway. The effect of lncNEAT1 in DR and its regulations on miR-320a and HIF-1α were determined in a rat model of DR. RESULTS: HG treatment promoted the migration, invasion, and permeability of ARPE-19 cells. After lncNEAT1 silencing, HIF-1α, N-cadherin, and vimentin levels were downregulated, ZO-1 and occludin levels were upregulated, and the migration, permeability, and invasion of HG-treated ARPE-19 cells were inhibited. However, HIF-1α overexpression increased N-cadherin and vimentin expression, reduced ZO-1 and occludin expression, and promoted the migration, permeability, and invasion of ARPE-19 cells. The binding of miR-320a with both lncNEAT1 and HIF-1α was predicted and confirmed. In a diabetic rat model, silencing lncNEAT1 inhibited HIF-1α/ANGPTL4/p-STAT3 pathway activation and alleviated retinopathy. CONCLUSIONS: The lncNETA1/miR-320a/HIF-1α ceRNA network activates the ANGPTL4/p-STAT3 pathway and promotes HG-induced ARPE-19 cell invasion and migration. |
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