Long non-coding RNA CoroMarker regulates oxidized LDL-induced inflammatory injury via NF-κB/NLRP3 signaling pathway

LIU Gang; HU Xun; LI Yi; LONG Ming

摘要：Background Long noncoding RNAs(lncRNAs)are considered to be important for the development and pro-gression of atherosclerosis.The lncRNA AC 100865.1(referred to as CoroMarker)has been recognized a novel and specific biomarker of coronary artery disease.However,its underlying molecular mechanisms remain unclear.Objective:The aim of this study was to investigate the implication of CoroMarker in oxidized low-density lipopro-tein(ox-LDL)-induced apoptosis and inflammation in THP-1 cells.The regulatory relationship between CoroMark-er and the nuclear factor kappa B(NF-κB)/NOD-like receptor protein 3(NLRP3)pathway was also explored.Methods:THP-1 cells were stimulated with ox-LDL to induce inflammatory injury.The expression of CoroMarker was silenced by small interfering RNA.Cell apoptosis were assessed by flow cytometry.Inflammatory response was determined by detecting levels of inflammatory cytokines using quantitative real-time polymerase chain reac-tion(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA).Furthermore,western blot was used to assess the expression of NF-κB/NLRP3 signaling pathway-related proteins.Results:Ox-LDL markedly induced cell inju-ry by promoting cell apoptosis,oxidative stress,and inflammation.Meanwhile,the expression of CoroMarker was also up-regulated in ox-LDL-injured THP-1 cells.The knockdown of CoroMarker reduced apoptosis rate and sig-nificantly changed the expression levels of apoptosis-related genes(Bax and BCL-2).In addition,knockdown of CoroMarker relieved oxidative stress by significant changes in the level of malondialdehyde,superoxide dis-mutase,and reactive oxygen species,and attenuated inflammatory injury by inhibit the production of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor alpha(TNF-α).Importantly,the suppression of CoroMarker decreased the expression of NF-κB/NLRP3 signaling pathway-related proteins,including p-NF-κB,p-IkBα and NLRP3.Conclusion:This study demonstrated that downregulation of CoroMarker alleviated ox-LDL-induced oxidative stress and inflammatory injury in THP-1 cells,possibly by modulating the NF-κB/NLRP3 signaling pathway.