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LncRNA ZEB1-AS1 facilitates ox-LDL-induced damage of HCtAEC cells and the oxidative stress and inflammatory events of THP-1 cells via miR-942/HMGB1 signaling.

AIMS The role of long noncoding RNA ZEB1 antisense 1 (lncRNA ZEB1-AS1) in carotid artery atherosclerosis remains barely explored. MATERIALS AND METHODS The viability and apoptosis of HCtAEC cells were… Click to show full abstract

AIMS The role of long noncoding RNA ZEB1 antisense 1 (lncRNA ZEB1-AS1) in carotid artery atherosclerosis remains barely explored. MATERIALS AND METHODS The viability and apoptosis of HCtAEC cells were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Caspase-3 activity detection assay and flow cytometry. The oxidative stress status and inflammation of THP-1 cells were detected by oxidative stress indicator detection kit and Enzyme-linked immunosorbent assay (ELISA). The abundance of ZEB1-AS1, miR-942 and high-mobility group box 1 (HMGB1) was measured by quantitative real time polymerase chain reaction (qRT-PCR). The targets of ZEB1-AS1 and miR-942 in HCtAEC and THP-1 cells were predicted by DIANA tool, and the combination was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot was conducted to examine the protein expression of HMGB1. KEY FINDINGS ZEB1-AS1 promoted ox-LDL-mediated injury in HCtAEC and THP-1 cells. MiR-942 was a direct target of ZEB1-AS1, and it was negatively modulated by ZEB1-AS1 in HCtAEC and THP-1 cells. HMGB1 could bind to miR-942, and it was regulated by ZEB1-AS1/miR-942 axis in HCtAEC and THP-1 cells. HMGB1 overexpression or miR-942 depletion reversed the inhibitory effects of ZEB1-AS1 intervention on the injury and apoptosis of HCtAEC cells and the oxidative stress and inflammation of THP-1 cells. SIGNIFICANCE LncRNA ZEB1-AS1 contributed to ox-LDL-mediated injury and apoptosis of HCtAEC cells and the oxidative stress and inflammation of THP-1 cells through up-regulating HMGB1 via sponging miR-942. ZEB1-AS1/miR-942/HMGB1 axis might provide a new direction to treatment carotid artery atherosclerosis.

Keywords: zeb1 as1; hctaec; mir 942; thp cells

Journal Title: Life sciences
Year Published: 2020

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