Knockdown of GAS5 restores ox-LDL-induced impaired autophagy flux via upregulating miR-26a in human endothelial cells

BackgroundOxidized low-density lipoprotein (ox-LDL)-induced endothelial cell (EC) injury and autophagy dysfunction play a vital role in the development of atherosclerosis. LncRNAs have been identified to participate in the regulation of pathogenesis of atherosclerosis. However, it remains largely undefined whether growth-arrest specific transcript 5 (GAS5) could influence ox-LDL-induced autophagy dysfunction in ECs.\n\nMethodsThe expressions of GAS5 and miR-26a in the plasma samples of patients with atherosclerosis and ox-LDL-treated human aortic endothelial cells (HAECs) were detected by qRT-PCR. Luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull down were performed to validate whether GAS5 could directly interact with miR-26a. The effects of ox-LDL, GAS5 or combined with miR-26a on apoptosis and autophagy were evaluated by flow cytometry analysis and western blot, respectively.\n\nResultsGAS5 expression was upregulated and miR-26a was downregulated in the plasma samples of patients with atherosclerosis and ox-LDL-treated HAECs. There was reciprocal inhibition between GAS5 and miR-26a expressions in ox-LDL-treated HAECs. We further demonstrated that GAS5 directly interacted with miR-26a in ox-LDL-treated HAECs. Additionally, ox-LDL administration induced apoptosis and impaired autophagy flux in HAECs. Rescue experiments demonstrated that GAS5 knockdown restored ox-LDL-induced impaired autophagy flux by upregulating miR-26a in HAECs.\n\nConclusionKnockdown of GAS5 restores ox-LDL-induced impaired autophagy flux via upregulating miR-26a in human endothelial cells, revealing a novel regulatory mechanism for ox-LDL-induced impaired autophagy flux in ECs through ceRNA crosstalk.