LncRNA ATP2B1‐AS1 modulates endothelial permeability via regulating miR‐4729/IQGAP2 axis in diabetic retinopathy

Mounting evidences indicate that long none coding RNAs (lncRNAs) are important to modulate biological process of diabetic retinopathy (DR). We aim to investigate the role of lncRNAs in DR and elucidate the exact mechanism.Real-time quantitive PCR was performed to distinguish the lncRNA ATPase plasma membrane Ca2+ transporting 1 antisense RNA 1 (ATP2B1-AS1) expression in DR patients and high-glucose-treated human retinal endothelial cells (HRECs). Dual-luciferase reporter system was used to verify that ATP2B1-AS1 could act as a miR-4729 sponge and miR-4729 could bind to 3'UTR of IQ motif-containing GTPase-activating protein 2 (IQGAP2). Cell proliferation assay, wound healing migration assay, transwell assay, tube formation assay and immunofluorescence were used to investigate cell proliferation, migration and angiogenesis in HRECs.Our results indicated that ATP2B1-AS1 was downregulated in DR patients and high-glucose-induced HRECs. In gain-and loss-of-function assays, ATP2B1-AS1 overexpression could significantly reduce cell proliferation, migration, angiogenesis and permeability induced by high glucose in vitro. Additionally, we performed dual-luciferase reporter experiments to determine that ATP2B1-AS1 could as a miR-4729 sponge. ATP2B1-AS1 overexpression could rescue miR-4729 mimics and shRNA-IQGAP2 induced cell proliferation, migration and angiogenesis in HRECs.Our study indicates that ATP2B1-AS1 acts as a miR-4729 sponge to regulate IQGAP2 reduce high-glucose-induced endothelial dysfunction in DR.