Long non-coding ribonucleic acid ATP2B1-AS1 modulates endothelial permeability through regulating the miR-4729-IQGAP2 axis in diabetic retinopathy.

Abstract

ABSTRACTAims/IntroductionMounting evidence shows that long non‐coding RNAs (lncRNAs) are important to modulate the biological process of diabetic retinopathy (DR). We aimed to investigate the role of lncRNAs in DR and elucidate the exact mechanism.Materials and MethodsReal‐time quantitative polymerase chain reaction was carried out to distinguish the lncRNA ATPase plasma membrane Ca2+ transporting 1 antisense RNA 1 (ATP2B1‐AS1) expression in DR patients and HG‐treated human retinal endothelial cells (HRECs). Dual‐luciferase reporter system was used to verify that ATP2B1‐AS1 could act as a microRNA (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.ResultsThe present results showed 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 carried out dual‐luciferase reporter experiments to determine that ATP2B1‐AS1 could act as a miR‐4729 sponge. ATP2B1‐AS1 overexpression could rescue miR‐4729 mimics and short hairpin RNA‐IQGAP2 induced cell proliferation, migration and angiogenesis in HRECs.ConclusionsThe present study showed that ATP2B1‐AS1 acted as a miR‐4729 sponge to regulate IQGAP2 reducing high‐glucose‐induced endothelial dysfunction in DR.