Downregulation of Nur77 accelerates lung adenocarcinoma cells apoptosis and autophagy through the inhibition of the PI3K/AKT pathway
Objective:To investigate the role and mechanism of Nur77 in lung adenocarcinoma cell apoptosis and autophagy.Methods:Five cases of lung adenocarcinoma tissues which were confirmed by pathology and para-cancerous tissues were collected from the Affiliated Southwest Hospital of Youjiang Medical University for Nationalities(People's Hospital of Baise).The expres-sion of Nur77 in lung adenocarcinoma and para-cancerous tissues was detected with immunofluorescence.Nur77-associated path-ways were analyzed with bioinformatics analysis.Human bronchial epithelial(BEAS-2B)cells and human lung cancer(A549)cells were cultured in vitro and designated as BEAS-2B and A549 groups,respectively.In both groups,Nur77 mRNA expression was measured with RT-qPCR,the expression of Nur77,LC3,PI3K,p-PI3K,AKT,and p-AKT was assessed with western blotting,and the fluorescence intensity of Nur77 was determined with immunofluorescence.A549 cells were transfected with si-NC or si-Nur77,referred to as si-NC or si-Nur77 groups,respectively,and non-transfected cells serving as the control group(Con).Nur77 expression was analyzed with RT-qPCR,and the expression of Nur77,LC3,PI3K,p-PI3K,AKT,p-AKT,cas-pase-3,Bax,and Bcl-2 was examined using Western blot.Cell apoptosis was assessed by flow cytometry.Results:Lung adenocar-cinoma tissues exhibited higher levels of Nur77 protein expression compared to para-cancerous tissues.Bioinformatics analysis demonstrated a correlation between Nur77 and the PI3K/AKT pathway.The mRNA and protein expression of Nur77(P<0.001)and the ratio of LC3Ⅱ/LC3Ⅰ,p-AKT/AKT(P<0.05),and p-PI3K/PI3K(P<0.01)were higher in the A549 group than in the BEAS-2B group.Compared with the si-NC group,the si-Nur77 group exhibited decreased Bcl-2 expression(P<0.05),in-creased Caspase-3 and Bax expression(P<0.01),and elevated LC3Ⅱ/LC3Ⅰ ratio(P<0.01),along with reduced p-AKT/AKT(P<0.05)and p-PI3K/PI3K(P<0.01)ratios and significantly enhanced apoptosis(P<0.05).Conclusion:Nur77 down-regulation accelerates autophagy and apoptosis in lung cancer cells,which may be achieved by the inhibition of the PI3K/AKT pathway.
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