Long noncoding RNA ZRANB2-AS2 promotes endothelial cell dysfunction by inhibiting phosphorylation of acetyl-CoA carboxylase 1 in diabetes

Abstract

LncRNA has been implicated in the regulation of diabetes. We identified a novel lncRNA that inhibits phosphorylation of acetyl-CoA carboxylase 1 to modulate the dysfunction of vascular endothelial cells under high glucose conditions. In vitro experiments were performed to investigate the effects of lnc RNA ZRANB2-AS2 on ACC1 phosphorylation, free fatty acid and triglyceride levels, angiogenesis, cell apoptosis, cell proliferation and migration rate. Further, in vivo experiments were designed to examine the effects of lnc RNA ZRANB2-AS2 on the level of ACC1, the limb ischemia and foot movement of mice, as well as on apoptosis, cell proliferation, and migration of vascular endothelial cells under conditions of high glucose.By RNA sequencing, we identified a lncRNA, ZRANB2-AS2, which is highly expressed in human umbilical vein endothelial cells (HUVECs) under high glucose condition. We demonstrated that it could promote apoptosis and inhibit angiogenesis, proliferation and migration of endothelial cells. Using RNA pull-down and RIP assays, the binding specificity of lncRNA ZRANB2-AS2 and acetyl-CoA carboxylase 1(ACC1) was determined. We further established the rescue assay by adding CMS-121, a specific ACC1 inhibitor. These findings suggested that CMS-121 could reverse the inhibition of lncRNA ZRANB2-AS2 on ACC1 phosphorylation, decrease intracellular free fatty acid and triglyceride levels. We conducted in vivo experiments to determine the inhibitory effect of lncRNA ZRANB2-AS2 in diabetic mice model. Lnc ZRANB2-AS2 inhibits cell proliferation, migration and angiogenesis while accelerates apoptosis of endothelial cells by regulating the phosphorylation of acetyl-CoA carboxylase 1 in diabetes.