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 Bai.se). The expression of Nur77 in lung adenocarcinoma and para-cancerous tissues was detected with immunofluorescence. Nur77-associated pathways 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<((.((((1) and the ratio of LC3 II /LC3 I, p-AKT/AKT (P<((.((5), and p-PI3K/PI3K (P<((.((1) 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<((.((5), increased Caspase-3 and Bax expression (P<((.((1), and elevated LC3 I /LC3 I ratio (P<((.((1), along with reduced p-AKT/ AKT (P<((.((5) and p-PI3K/PI3K (P<((.((1) ratios and significantly enhanced apoptosis (P<((.((5).Conclusion: Nur77 down-regulation accelerates autophagy and apoptosis in lung cancer cells, which may be achieved by the inhibition of the PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]