上海交通大学学报（医学版）2025，Vol.45Issue(11)：1407-1420,14.DOI:10.3969/j.issn.1674-8115.2025.11.001
长非编码RNA LINC00467在肺腺癌中的表达及其影响肺腺癌进展的机制研究
Expression of long noncoding RNA LINC00467 and its mechanism in affecting lung adenocarcinoma progression
摘要
Abstract
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.关键词
长非编码RNA/LINC00467/肺腺癌/核因子κB/酪蛋白激酶2α2Key words
long noncoding RNA(lncRNA)/LINC00467/lung adenocarcinoma(LUAD)/nuclear factor kappa-B(NF-κB)/casein kinase 2 alpha 2(CSNK2A2)分类
医药卫生引用本文复制引用
GUO Linyan,ZHANG Hailong,ZHENG Chao,LEI Ming..长非编码RNA LINC00467在肺腺癌中的表达及其影响肺腺癌进展的机制研究[J].上海交通大学学报（医学版）,2025,45(11):1407-1420,14.基金项目
国家自然科学基金(82403599). National Natural Science Foundation of China(82403599). （82403599）
