LncRNA ZEB1-AS1 knockdown alleviates oxidative low-density lipoprotein-induced endothelial cell injury via the miR-590-5p/ HDAC9 axis

• Published in: Central-European journal of immunology Vol. 46; no. 3; pp. 325 - 335
• Main Authors: Zhong, Jinpeng, Cheng, Bin, Yang, Li, Li, Guanlan, Yuan, Yunzhong, Luo, Gang, Shu, Zhiping, Jiang, Hong
• Format: Journal Article
• Language: English
• Published: Warsaw Termedia Publishing House 01-01-2021
• Subjects: Annexin V; Apoptosis; Arteriosclerosis; Atherosclerosis; Caspase-3; Cell injury; Cell proliferation; Endothelial cells; Experimental Immunology; hdac9; lncrna zeb1-as1; Low density lipoprotein; mir-590-5p; Non-coding RNA; ox-ldl; Poly(ADP-ribose) polymerase; Polymerase chain reaction; Tumor necrosis factor; Tumor necrosis factor-TNF
• ISSN: 1426-3912; 1644-4124
• DOI: 10.5114/ceji.2021.108767

Oxidative low-density lipoprotein (ox-LDL) is thought to induce vascular endothelial cell injury, which contributes to the aetiopathogenesis of atherosclerosis (AS). Several previous reports have identified that lncRNA ZEB1-AS1 participates in the regulatory mechanisms of endothelial cell injury, but the potential interaction mechanism between ZEB1-AS1 and miR-590-5p in ox-LDL-induced endothelial cell damage is not clear. ZEB1-AS1 and miR-590-5p expression were tested by quantitative real-time polymerase chain reaction (qRT-PCR) in ox-LDL-treated endothelial cells. The proliferation and apoptosis were determined by MTT and Annexin V/PI double-staining assay, respectively. The protein expression of HDAC9, tumor necrosis factor  (TNF-), cleaved caspase-3, and cleaved PARP were measured by western blot analysis. Dual-luciferase reporter and RIP assays affirmed the functional targets of ZEB1-AS1. ZEB1-AS1 expression was upregulated in ox-LDL-treated HUVECs, and miR-590-5p was lessened in a dose- or time-depended manner, respectively. Knockdown of ZEB1-AS1 facilitated ox-LDL-treated endothelial cell proliferation and inhibited cell apoptosis. Moreover, miR-590-5p was directly targeted via ZEB1-AS1 in ox-LDL-treated HUVECs. ZEB1-AS1 silencing attenuated ox-LDL-induced cell injury via regulation of miR-590-5p expression. Furthermore, HDAC9 reversed the influence of miR-590-5p on propagation and apoptosis of ox-LDL-induced endothelial cells. Knockdown of ZEB1-AS1 alleviates ox-LDL-induced endothelial cell injury by regulating the miR-590-5p/HDAC9 axis.