目的·探究长非编码RNA（long noncoding RNA，lncRNA）LINC00467在肺腺癌（lung adenocarcinoma，LUAD）中的表达情况及其对患者不良预后的影响，并揭示其调控LUAD发生发展的作用及潜在分子机制。方法·首先，利用癌症基因组图谱（The Cancer Genome Atlas，TCGA）数据库中的肿瘤样本数据，分析LINC00467在LUAD组织中的表达水平及其与患者生存期的相关性。其次，构建LINC00467稳定敲低LUAD细胞系，通过细胞表型实验（即活细胞成像检测细胞增殖实验、平板克隆形成实验、细胞划痕实验）及裸鼠皮下成瘤实验，评估LINC00467对LUAD细胞增殖、克隆形成、迁移及成瘤能力的影响。进一步，通过转录组测序（RNA sequencing，RNA-seq）技术、差异表达基因（differentially expressed gene，DEG）分析和hallmark gene sets富集分析，探究LINC00467调控肿瘤细胞的相关信号通路，并利用蛋白质印迹法（Western blotting）验证其对肿瘤细胞通路的影响。最后，通过RNA pull-down联合蛋白质谱以及免疫共沉淀（co-immunoprecipitation，co-IP）实验，筛选并验证LINC00467的相互作用蛋白。结果·TCGA数据库的肿瘤样本数据的分析结果表明LINC00467在LUAD中异常高表达，且其表达水平与LUAD患者的生存期呈负相关（P=0.004）。细胞表型实验及裸鼠皮下成瘤实验的结果均显示，敲低LINC00467可显著抑制LUAD细胞的增殖、克隆形成、迁移和体内成瘤的能力（均P<0.05）。RNA-seq、DEG分析、hallmark gene sets富集分析及蛋白质印迹的结果均表明，敲低LINC00467可抑制核因子κB（nuclear factor kappa-B，NF-κB）信号通路的激活。RNA pull-down联合蛋白质谱和co-IP的结果表明LINC00467与酪蛋白激酶2α2（casein kinase 2 alpha 2，CSNK2A2）存在相互作用，并促进NF-κB p65的磷酸化。结论·LINC00467在LUAD组织中的高表达与患者预后呈负相关；LINC00467可以与CSNK2A2相互作用，促进NF-κB p65的磷酸化，激活NF-κB通路，促进LUAD增殖、克隆形成、迁移和体内成瘤。

Objective ·To investigate the expression of long noncoding RNA (lncRNA) LINC00467 in lung adenocarcinoma (LUAD) and its impact on the poor prognosis of patients, as well as its functional role and underlying molecular mechanisms in the occurrence and development of LUAD. Methods ·First, tumor sample data from The Cancer Genome Atlas (TCGA) database were utilized to analyze the expression levels of LINC00467 in LUAD tissues and its correlation with patient survival. Second, a stable LINC00467-knockdown LUAD cell line was established, and the effects of LINC00467 on LUAD cell proliferation, colony formation, migration, and tumorigenicity were assessed through cell phenotypic experiments (including live-cell imaging for cell proliferation analysis, plate colony formation assays, and wound healing assays) and nude mouse tumor formation experiments. Furthermore, RNA sequencing (RNA-seq), differentially expressed genes (DEGs) analysis, and hallmark gene sets enrichment analysis were performed to identify signaling pathways regulated by LINC00467, and Western blotting was used to validate its impact on tumor cell pathways. Finally, RNA pull-down combined with mass spectrometry and co-immunoprecipitation (co-IP) assays were conducted to filter and identify LINC00467-interacting proteins. Results ·Analysis of tumor sample data from the TCGA database showed that LINC00467 was highly expressed in LUAD, and its expression level was negatively correlated with overall survival in LUAD patients (P=0.004). Cell phenotypic experiments and nude mouse tumor formation experiments demonstrated that LINC00467 knockdown significantly inhibited the proliferation, colony formation, migration and in vivo tumorigenesis of LUAD cells (all P<0.05). RNA-seq, DEGs analysis, hallmark gene sets enrichment analysis, and Western blotting indicated that knockdown of LINC00467 suppressed the activation of nuclear factor kappa-B (NF-κB) signaling pathway. RNA pull-down combined with mass spectrometry and co-IP assays demonstrated that LINC00467 interacted with casein kinase 2 alpha 2 (CSNK2A2) and promoted the phosphorylation of NF-κB p65. Conclusion ·High expression of LINC00467 in LUAD tissues is negatively correlated with patient prognosis. LINC00467 can interact with CSNK2A2, promote the phosphorylation of NF-κB p65, activate the NF-κB pathway, and enhance LUAD proliferation, colony formation, migration, and in vivo tumorigenesis.