DARS2在非小细胞肺癌中的表达及其对细胞增殖和迁移的影响  

Expression of DARS2 in non-small cell lung cancer and its effect on proliferation and migration

作　　者：艾尼瓦尔·肉孜 韩林晓 吴圆圆 朱文思 刘静[4] 刘尽国 周建[1,2,3] ROUZI Ainiwaer;HAN Lin-xiao;WU Yuan-yuan;ZHU Wen-si;LIU Jing;LIU Jin-guo;ZHOU Jian(Department of Pulmonary and Critical Care Medicine,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Shanghai Engineering Research Center of Internet of Things for Respiratory Medicine,Shanghai 200032,China;Shanghai Respiratory Research Institute,Shanghai 200032,China;Department of Pathology,Yantai Yuhuangding Hospital,Qingdao Medical College,Qingdao University,Yantai 264000,Shandong Province,China;Department of Oncology,Tenth People's Hospital of Tongji University-Tongji University Cancer Center,Shanghai 200072,China)

机构地区：[1]复旦大学附属中山医院呼吸与危重症医学科,上海200032 [2]上海呼吸物联网医学工程技术研究中心,上海200032 [3]上海市呼吸病研究所,上海200032 [4]青岛大学青岛医学院附属烟台毓璜顶医院病理科,烟台264000 [5]同济大学附属第十人民医院肿瘤科-同济大学癌症中心,上海200072

出　　处：《复旦学报（医学版）》2023年第3期390-397,共8页Fudan University Journal of Medical Sciences

基　　金：上海市科委上海工程技术研究中心建设计划(20DZ2254400);上海市临床重点专科建设项目(shslczdzk02201)。

摘　　要：目的探究线粒体天冬氨酰-tRNA合成酶2(aspartyl-tRNA synthetase 2,mitochondrial,DARS2)在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及生物学意义。方法采用多种数据库分析DARS2在NSCLC的两种亚型肺腺癌(lung adenocarcinoma,LUAD)和肺鳞癌(lung squamous cellcarcinoma,LUSC)中的表达水平、预后价值、临床病理分期相关性、突变及甲基化水平和富集通路。通过划痕实验和CCK-8实验进一步分析DARS2对NSCLC细胞增殖和迁移能力的影响。结果通过GEPIA、GEO及HPA数据库分析发现,DARS2 mRNA和蛋白质表达水平在LUAD与LUSC中均显著上调,并与LUAD病理分期呈正相关。生存分析结果表明,DARS2过表达可显著缩短LUAD患者生存期。cBioPortal分析结果显示,DARS2在LUAD与LUSC中变异率分别为16%和18%。UALCAN数据库甲基化分析结果显示,DARS2启动子区域甲基化水平在LUAD中显著降低,而在LUSC中显著升高。Metascape数据库富集分析结果显示,与DARS2相关的基因在LUAD和LUSC中均主要在细胞周期通路高度富集。划痕实验和CCK-8实验结果显示,敲低DARS2能显著抑制H1299细胞增殖和迁移能力。结论DARS2在LUAD与LUSC中均过表达,其可能以参与调控细胞周期通路方式促进NSCLC细胞增殖和迁移。Objective To investigate the expression level and biological significance of aspartyl-tRNA synthetase 2,mitochondrial(DARS2)in non-small cell lung cancer(NSCLC).Methods DARS2 expression levels,prognostic value,clinicopathological staging correlation,mutation and methylation levels,and enrichment pathways in lung adenocarcinoma(LUAD)and lung squamous cell carcinoma(LUSC),the two major subtypes of NSCLC,were investigated using various databases.On this basis,the effect of DARS2 on the proliferation and migration ability of NSCLC cells was further analyzed by scratch assay and CCK-8 assay.Results GEPIA,GEO,and HPA database analysis results showed that DARS2 mRNA and protein expression levels were significantly upregulated in LUAD and LUSC,and DARS2 mRNA expression levels were positively correlated with pathological stage in LUAD.Survival analysis showed that patients with high DARS2 expression in LUAD had shorter survival times.cBioPortal analysis showed that DARS2 variability was 16%in LUAD and 18%in LUSC,respectively.UALCAN database methylation analysis showed that the methylation level of the DARS2 promoter region was significantly lower in LUAD and considerably higher in LUSC.Metascape database results showed that DARS2-related genes were highly enriched in both LUAD and LUSC,mainly in the cell cycle pathway.The results of scratch and CCK-8 assays showed that the knockdown of DARS2 significantly inhibited the proliferation and migration ability of H1299 cells.Conclusion DARS2 is overexpressed in LUAD and LUSC and may promote the proliferation and migration of NSCLC cells by participating in cell cycle regulation.

关 键 词：肺腺癌(LUAD) 肺鳞癌(LUSC) 天冬氨酰-tRNA合成酶2(DARS2) 增殖 迁移 细胞周期 

分 类 号：R734.2[医药卫生—肿瘤]