NPM3在肺腺癌中的表达及其对肺腺癌细胞生物学功能的影响  

Expression of NPM3 in Lung Adenocarcinoma and Its Impact on the Biological Function of Lung Adenocarcinoma Cells

作　　者：王韵[1,2] 舒扬[2] 武晓白 郭若楠 黄汉鹏[1] 向敏 Wang Yun;Shu Yang;Wu Xiaobai(Department of Pulmonary and Critical Care Medicine,Affiliated Hospital of Jiangsu University,Zhenjiang 212001,China;Central Laboratory,Affiliated Hospital of Jiangsu University,Zhenjiang 212001,China)

机构地区：[1]江苏大学附属医院呼吸与危重症医学科,镇江212001 [2]江苏大学附属医院中心实验室,镇江212001 [3]江苏大学附属医院检验科,镇江212001

出　　处：《华中科技大学学报(医学版)》2025年第1期36-44,共9页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：江苏省镇江“169工程”培养对象科研项目(No.YLJ202105);镇江市社会发展指导性科技计划项目(No.FZ2023055);镇江市重点研发计划资助项目(No.SH2023003)

摘　　要：目的探究Nucleophosmin3(NPM3)在肺腺癌中的表达情况及其对肺腺癌细胞系H292生物学功能的影响,为肺腺癌的诊疗提供新的思路。方法首先利用生物信息学数据库TCGA分析NPM3基因在肺腺癌和正常组织中的表达差异及其与肺腺癌患者临床病理特征和预后的相关性;通过基因干扰技术构建敲低NPM3的细胞模型(si-NPM3-H292),运用实时荧光定量PCR技术(qRT-PCR)和蛋白免疫印迹技术(Westernblot)检测干扰效率;通过CCK-8及平板克隆实验检测敲低NPM3对肺腺癌细胞增殖能力的改变;运用划痕实验和Transwell实验检测敲低NPM3对H292细胞迁移能力的影响;运用qRT-PCR法和Westernblot检测与上皮间质转化(EMT)相关指标的mRNA及蛋白表达情况;通过Westernblot检测PI3K/Akt信号通路相关蛋白的表达水平。结果TCGA数据库分析结果显示,NPM3在肺腺癌中高表达且与肺腺癌患者临床病理分型密切相关,高表达NPM3的肺腺癌患者的生存预后显著差于低表达NPM3的患者(P<0.05)。成功构建敲低NPM3的细胞模型;敲低NPM3的表达降低了H292细胞的增殖和迁移能力(均P<0.05);与对照组比较,si-NPM3-H292细胞中E-cadherin的mRNA及蛋白表达水平均上调,N-cadherin的mRNA及蛋白表达水平均下调(均P<0.05);与对照组比较,si-NPM3-H292细胞中Akt及PI3K的蛋白表达水平无明显变化,但其磷酸化水平降低,而PTEN的蛋白表达水平有所上升(均P<0.05)。结论NPM3在肺腺癌中高表达且与患者不良预后相关,NPM3可能通过调控PI3K/Akt信号通路发挥对肺腺癌细胞增殖与迁移的促进作用。Objective To investigate the expression of Nucleophosmin 3(NPM3)in lung adenocarcinoma and its impact on the biological functions of the lung adenocarcinoma cell line H292,with the goal of providing innovative insights for the diagno-sis and therapeutic strategies of lung adenocarcinoma.Methods The differential expression of the NPM3 gene between lung ad-enocarcinoma and normal controls was analyzed,along with its correlation with the clinicopathological characteristics and prog-nosis of lung adenocarcinoma patients,using the TCGA bioinformatics database.A cell model with reduced NPM3 expression(si-NPM3-H292)was developed by gene interference technology,and the efficiency of this knockdown was assessed by real-time fluorescence quantitative PCR(qRT-PCR)and Western blotting.The impact of NPM3 knockdown on the proliferative capacity of lung adenocarcinoma cells was evaluated by using CCK-8 and plate clone formation assays.The scratch and Transwell assays were employed to assess the effect of NPM3 knockdown on the migratory potential of H292 cells.The mRNA and protein ex-pression levels of markers associated with epithelial-mesenchymal transition(EMT)were determined by qRT-PCR and Western blotting.Additionally,the expression levels of proteins involved in the PI3K/Akt signaling pathway were examined by Western blotting.Results Analysis of the TCGA database indicated that NPM3 is highly expressed in lung adenocarcinoma and is sig-nificantly associated with the clinicopathological classification of lung adenocarcinoma patients.The survival outcomes for pa-tients with high NPM3 expression were notably worse than those with low expression(P<0.05).The knockdown cell model was successfully established,and the proliferation and migration capabilities of H292 cells were significantly diminished after NPM3 knockdown(P<0.05).Compared to the control group,mRNA and protein levels of E-cadherin were increased in si-NPM3-H292 cells,while the expression level of N-cadherin was reduced at both mRNA and protein levels(P<0.05).Althou

关 键 词：NPM3 肺腺癌 上皮间质转化 细胞增殖 细胞迁移 

分 类 号：R734.2[医药卫生—肿瘤]