电压门控钾通道亚家族G成员1在肺癌中的表达及生物学作用  

Expression and biological role of potassium voltage-gated channel subfamily G member 1 in lung cancer

作　　者：程峰 彭诗晴 曹杨 陆益民[2] CHENG Feng;PENG Shiqing;CAO Yang;LU Yimin(School of Medicine,Jiangsu University,Zhenjiang Jiangsu 212013;Pulmonary and Critical Care Medicine,Kunshan Hostipal Affiliated to Jiangsu University,Suzhou Jiangsu 215300,China)

机构地区：[1]江苏大学医学院,江苏镇江212013 [2]江苏大学附属昆山医院呼吸与危重症医学,江苏苏州215300

出　　处：《江苏大学学报（医学版）》2023年第6期475-485,共11页Journal of Jiangsu University：Medicine Edition

基　　金：江苏省卫生厅科技项目(YG201403);苏州市医学重点学科基金资助项目(SZXK201821)。

摘　　要：目的:探讨电压门控钾通道亚家族G成员1(potassium voltage-gated channel subfamily G member 1,KCNG1)在人肺癌组织中的表达水平和临床意义以及其在肺癌细胞恶性生物学行为中的作用。方法:通过TCGA数据库(The Cancer Genome Atlas)分析KCNG1 mRNA在人肺癌组织中的表达水平,探究其与肺癌患者临床病理特征及预后的关系;基于KCNG1 mRNA表达水平构建预测肺癌患者预后的列线图模型;采用基因本体(GO)功能富集分析和京都基因与基因组百科全书通路(KEGG)富集分析探究KCNG1潜在的生物学功能;采用基因集富集分析(GSEA)预测KCNG1相关差异表达基因参与调控的相关信号通路。采用实时荧光定量PCR(qRT-PCR)及蛋白免疫印迹分别检测肺癌A549和H1299细胞系以及正常肺上皮细胞中KCNG1 mRNA和蛋白表达水平;通过转染siRNA构建KCNG1敲减的细胞株,分别采用EdU,Transwell,Matrigel Transwell,细胞划痕愈合及血管生成拟态实验检测细胞株生物学行为变化。结果:KCNG1 mRNA在肺癌组织中显著高表达且与肺癌患者不良预后密切相关(P均<0.05);列线图模型初步证实KCNG1可能是肺癌潜在的生物标志物,并具有良好的预后评价功能;GO及KEGG富集分析提示KCNG1在调节激素分泌、离子转运、神经肽信号通路及细胞间黏附等生物学过程中发挥重要作用;GSEA结果提示KCNG1相关差异表达基因主要富集在KRAS,MTORC1,MYC,P53及WNT信号通路;KCNG1敲低的肺癌细胞增殖、迁移、侵袭和成管能力明显受到抑制(P均<0.05)。结论:KCNG1 mRNA在肺癌中显著高表达且与患者不良预后密切相关;siRNA介导的KCNG1敲低可显著抑制肺癌细胞的恶性生长。Objective:To investigate the expression level and clinical significance of potassium voltage-gated channel subfamily G member 1(KCNG1)in human lung cancer tissues,and its role in the malignant biological behavior of lung cancer cells.Methods:The Cancer Genome Atlas(TCGA)database was consulted to explore the expression level of KCNG1 mRNA in human lung cancers,and the relationship between KCNG1 mRNA and clinicopathological features and prognosis of patients with lung cancer;nomogram model was constructed to predict the prognosis of lung cancer patients based on the KCNG1 mRNA expression;Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to explore the potential biological functions of KCNG1;gene set enrichment analysis(GSEA)was employed to analyze the differentially expressed genes,through comparing KCNG1 high-expression lung cancer tissues with the KCNG1 low-expression lung cancer tissues retrieved from TCGA database.The expression level of KCNG1 mRNA and protein in lung cancer A549 and H1299 cell lines and normal lung epithelial cells were detected by Western blotting and qRT-PCR assays,respectively.The KCNG1 knockdown cell lines were constructed by transfection of siRNA,and the biological behavior changes of the cell lines were detected by EdU,Transwell,Matrigel Transwell,scratch wound healing and angiogenesis mimicry tests,respectively.Results:The expression of KCNG1 mRNA was significantly upregulated in human lung cancer tissues and was correlated with poor prognosis of lung cancer patients(P<0.05).The nomogram model preliminarily confirmed that KCNG1 may be a potential biomarker of lung cancer and has a good prognostic function.GO and KEGG enrichment analysis suggested that KCNG1 plays an important role in regulating hormone secretion,ion transportation,neuropeptide signaling pathway,and intercellular adhesion.GSEA showed that KCNG1 related differentially expressed genes were enriched in KRAS,MTORC1,MYC,P53,and WNT signaling pathways.The p

关 键 词：肺癌 电压门控钾通道亚家族G成员1 分子靶标 差异表达基因 生物标志物 

分 类 号：R734.2[医药卫生—肿瘤]