长链非编码RNA DLGAP1-AS2在胃癌中的表达及其作用机制  

Expression and mechanism of long non-coding RNA DLGAP1-AS2 in gastric cancer

作　　者：陆佳伟 唐银炳 张伟亚 张守亮[1] 祁卫东[1] 马圭[1] 张文波[1] 蒋鹏程[1] LU Jiawei;TANG Yinbing;ZHANG Weiya;ZHANG Shouliang;QI Weidong;MA Gui;ZHANG Wenbo;JIANG Pengcheng(Department of General Surgery,Affiliated People’s Hospital of Jiangsu University,Zhenjiang 212002,Jiangsu Province,China)

机构地区：[1]江苏大学附属人民医院普外科,江苏镇江212002

出　　处：《肿瘤》2020年第3期153-162,共10页Tumor

摘　　要：目的:探讨长链非编码RNA(long non-coding RNA,lncRNA)DLGAP1-AS2在胃癌中的表达及其临床意义。方法:从美国癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库下载胃腺癌相关数据集,分析肿瘤组织与正常组织中DLGAP1-AS2的表达差异。采用实时荧光定量PCR法测定85例胃癌组织及其相应癌旁组织,以及25例胃癌患者和25例健康者血浆中DLGAP1-AS2的表达水平,分析胃癌组织中DLGAP1-AS2表达水平与胃癌患者临床病理特征的相关性。通过转染小干扰RNA的方法敲减胃癌AGS细胞中DLGAP1-AS2的表达后,分别采用活细胞计数法、克隆形成实验及Transwell小室法检测下调DLGAP1-AS2对胃癌AGS细胞增殖、迁移和侵袭能力的影响,并采用蛋白质印迹法检测胃癌AGS细胞中上皮-间质转化(epithelial-mesenchymal transition,EMT)相关基因表达水平的变化。结果:TCGA数据库分析发现,DLGAP1-AS2在胃癌组织中的表达水平明显高于正常胃组织(P<0.001)。实时荧光定量PCR检测证实DLGAP1-AS2在胃癌组织中表达水平明显增高(P<0.05),并与肿瘤TNM分期、淋巴结转移和患者总生存率明显相关(P值均<0.05);而且DLGAP1-AS2在胃癌患者血浆中表达水平也明显增高(P<0.05)。敲减DLGAP1-AS2可抑制胃癌AGS细胞增殖、克隆形成、迁移及侵袭(P值均<0.05),并且明显下调基质金属蛋白酶2(matrix metalloproteinase 2,MMP2)、Slug、N钙黏蛋白(N-cadherin,N-cad)和Twist蛋白的表达水平(P值均<0.05)。结论:DLGAP1-AS2在胃癌患者癌组织及血浆中表达水平均明显增高。敲减DLGAP1-AS2能抑制胃癌细胞增殖、迁移及侵袭,其作用机制可能与调控EMT相关分子表达有关。Objective:To investigate the expression of long non-coding RNA(lncRNA)DLGAP1-AS2 in gastric cancer and its clinical significance.Methods:The data set of gastric adenocarcinoma was downloaded from The Cancer Genome Atlas(TCGA)database,and the difference of DLGAP1-AS2 expression between tumor tissues and normal tissues was analyzed.The tumor and adjacent tissues were collected from 85 gastric adenocarcinoma patients,and the plasma samples were collected from 25 gastric cancer patients and 25 healthy controls.Then the expression of DLGAP1-AS2 in tumor tissues and plasma samples was detected by real-time fluorescent quantitative PCR,and the correlation of the level of DLGAP1-AS2 with the clinicopathological features of gastric cancer patients was analyzed.Besides,after the transfection with DLGAP1-AS2 siRNA,the proliferation,migration and invasion of gastric cancer AGS cells were observed by viable cell counting method,colony formation assay and Transwell chamber assay,respectively.Moreover,the expressions of epithelial-mesenchymal transition(EMT)-related molecules after silencing DLGAP1-AS2 in AGS cells were detected by Western blotting.Results:The expression of DLGAP1-AS2 in gastric cancer tissues was higher than that in normal gastric epithelium according TCGA database(P<0.001).DLGAP1-AS2 was significantly overexpressed in gastric cancer tissues as compared with the corresponding paracancerous tissues,which was correlated with the advanced TNM stage,lymph node metastasis and overall survival rate(all P<0.05).While the level of DLGAP1-AS2 was also upregulated in the plasma of patients with gastric cancer as compared with the healthy(P<0.05).Knockdown of DLGAP1-AS2 expression inhibited the proliferation,colony formation,migration and invasion of gastric cancer AGS cells(all P<0.05).In addition,the expression levels of matrix metalloproteinase 2(MMP2),Slug,N-cadherin(N-cad)and Twist were significantly down-regulated in AGS cells transfected with DLGAP1-AS2 siRNA(all P<0.05).Conclusion:The expression of DLGAP1-AS2 is

关 键 词：胃肿瘤 RNA 长链非编码 上皮-间质转化 DLGAP1-AS2 

分 类 号：R735.2[医药卫生—肿瘤]