Regulation of Long Noncoding RNA NEAT1/miR-320a/HIF-1a Competitive Endogenous RNA Regulatory Network in Diabetic Retinopathy

PURPOSE. To determine the mechanism that long noncoding RNA NEAT1 (lncNEAT1)/miR320a competitive endogenous RNA (ceRNA) network regulates hypoxia-inducible factor-1a (HIF-1a) 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-1a, 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-1a by RIP assay. ARPE-19 cells were treated with lncNEAT1 or HIF-1a 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-1a 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-1a, 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-1a 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-1a was predicted and confirmed. In a diabetic rat model, silencing lncNEAT1 inhibited HIF-1a/ANGPTL4/p-STAT3 pathway activation and alleviated retinopathy.CONCLUSIONS. The lncNETA1/miR-320a/HIF-1a ceRNA network activates the ANGPTL4/p-STAT3 pathway and promotes HG-induced ARPE-19 cell invasion and migration.

Automated summary

This study reveals that the lncNEAT1/miR-320a/HIF-1a ceRNA network promotes HG-induced ARPE-19 cell invasion and migration through the activation of the ANGPTL4/p-STAT3 pathway.