海南医学院学报2024，Vol.30Issue(12)：897-904,8.DOI:10.13210/j.cnki.jhmu.20240403.001
下调Nur77抑制PI3K/AKT信号通路促进肺腺癌细胞凋亡和自噬
Downregulation of Nur77 accelerates lung adenocarcinoma cells apoptosis and autophagy through the inhibition of the PI3K/AKT pathway
摘要
Abstract
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.关键词
Nur77/肺腺癌/PI3K/AKT信号通路/凋亡/自噬Key words
Nur77/Lung adenocarcinoma/PI3K/AKT pathway/Autophagy/Apoptosis分类
医药卫生引用本文复制引用
莫黎芳,李小玲,韩谊,周娇,覃春艳,蒋玉洁..下调Nur77抑制PI3K/AKT信号通路促进肺腺癌细胞凋亡和自噬[J].海南医学院学报,2024,30(12):897-904,8.基金项目
This study was supported by the National Natural Science Foundation of China(81860021) （81860021）
the General Project of Guangxi Natural Science Foundation(2021GXNSFAA325003) （2021GXNSFAA325003）
the Research Basic Ability Improvement Project of Young and Middle-aged Teachers in Guangxi Universities(2021KY0540) （2021KY0540）
the Science Research and Technology Development Plan of Baise(20193117) （20193117）
the Scientific Research of High-level Talents of the Scientific Research and Training of High-Level Talents(Y202011722)国家自然科学基金资助项目(81860021) （Y202011722）
广西自然科学基金项目(2021GXNSFAA325003) （2021GXNSFAA325003）
广西高校中青年教师科研基础能力提升项目(2021KY0540) （2021KY0540）
百色市科学研究与技术开发计划(百科 20193117) （百科 20193117）
右江民族医学院附属医院 2020 年度高层次人次科研项目(Y202011722) （Y202011722）
