%0 Journal Article
%T Long non-coding ribonucleic acid ATP2B1-AS1 modulates endothelial permeability through regulating the miR-4729-IQGAP2 axis in diabetic retinopathy.
%A Ren Z
%A Wang X
%J J Diabetes Investig
%V 13
%N 3
%D Mar 2022
%M 34935307
%F 3.681
%R 10.1111/jdi.13740
%X <B>OBJECTIVE: </B>Mounting 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.<BR><B>METHODS: </B>Real-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.<BR><B>RESULTS: </B>The 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.<BR><B>CONCLUSIONS: </B>The present study showed that ATP2B1-AS1 acted as a miR-4729 sponge to regulate IQGAP2 reducing high-glucose-induced endothelial dysfunction in DR.