微小RNA-146a靶向Nm23-H1对胃印戒细胞癌侵袭和转移的影响  

Effect of microRNA-146a targeting Nm23-H1 on invasion and metastasis of gastric signet-ring cell carcinoma

作　　者：任柯[1] 刘清泉[1] 张亚猛 孙培春[2] Ren Ke;Liu Qingquan;Zhang Yameng;Sun Peichun(Department of Gastrointestinal Surgery,the First Affiliated Hospital of Luohe Medical College/Luohe Central Hospital,Luohe 462000,China;Department of Gastrointestinal Surgery,Henan Provincial People′s Hospital,Zhengzhou 450003,China)

机构地区：[1]漯河市医学高等专科第一附属医院/漯河市中心医院普外二科,462000 [2]河南省人民医院胃肠外科,郑州450003

出　　处：《中华实验外科杂志》2021年第3期442-445,共4页Chinese Journal of Experimental Surgery

基　　金：河南省医学科技攻关计划(联合共建)项目(LHGJ20191422)。

摘　　要：目的探讨微小RNA(miR)-146a靶向Nm23-H1对胃印戒细胞癌侵袭和转移的影响及其机制。方法选取2018年12月至2020年12月漯河市中心医院与河南省人民医院收治的49例胃低分化印戒细胞癌和对应癌旁组织作为研究对象。采用miRNA微阵列分析分析胃癌组织和癌旁组织差异表达miRNA;采用荧光定量聚合酶链反应验证胃癌组织和癌旁组织中差异表达miRNA;采用miRNA对照和miR-146a抑制剂慢病毒感染人胃印戒细胞癌细胞系HSC-39,建立对照(对照组)和miR-146a敲降细胞系(实验组)。采用Transwell分析两组细胞的侵袭能力;采用体内抑制瘤实验分析两组细胞的转移能力;采用生物信息学和双荧光素酶报告分析miR-146a的靶基因;采用蛋白质印迹法(Western blot)分析组织和组细胞系靶蛋白表达水平。组间数据比较采用t检验。结果肿瘤组织和癌旁组织差异表达的miRNA有84个,其中miR-146a是在肿瘤组织和癌旁组织中表达差异最大的miRNA。胃低分化印戒细胞癌组织miR-146a表达水平(2.96±0.31)高于癌旁组织miR-146a表达水平(1.29±0.23),差异有统计学意义(t=3.104,P<0.05)。实验组细胞miR-146a表达水平(0.33±0.15)低于对照组细胞miR-146a表达水平(1.02±0.19),差异有统计学意义(t=2.864,P<0.05)。实验组细胞侵袭数量[(32.12±4.14)个]低于对照组细胞侵袭数量[(81.45±8.09)个],差异有统计学意义(t=3.173,P<0.05)。实验组细胞淋巴结转移数量[(6.01±1.89)个]低于对照组细胞淋巴结转移数量[(13.50±3.09)个],差异有统计学意义(t=2.185,P<0.05)。Nm23-H1是miR-146a的靶蛋白。胃癌组织中Nm23-H1表达水平(0.36±0.11)低于癌旁组织中Nm23-H1表达水平(0.84±0.14),差异有统计学意义(t=2.850,P<0.05)。胃癌组织中Nm23-H1表达水平(0.92±0.13)低于对照组细胞Nm23-H1表达水平(0.27±0.08),差异有统计学意义(t=2.189,P<0.05)。结论miR-146a在印戒细胞型胃癌中呈高表达,通过靶向Nm23-H1调节胃印戒细胞�Objective To investigate the effect of microRNA(miR)-146a targeting nm23-H1 on invasion and metastasis of gastric signet-ring cell carcinoma and its molecular mechanism.Methods Totally 49 cases of poorly differentiated signet ring cell carcinoma of the stomach and corresponding adjacent tissues from December 2019 to December 2020 in Luohe Central Hospital and Henan Provincial People′s Hospital were selected as the research objects.miRNA microarray analysis was used to analyze the differentially expressed miRNAs in gastric cancer tissues and adjacent tissues.The differentially expressed miRNAs in gastric cancer tissues and adjacent tissues were verified by fluorescent quantitative polymerase chain reaction.Human gastric signet ring cell carcinoma cell line HSC-39 was infected with miRNA control and miR-146a inhibitor lentivirus to obtain stable cell line,serving as the control group and the experimental group,respectively.The invasion ability of the two groups was analyzed by Transwell.The metastasis ability of the two groups was analyzed by in vivo tumor inhibition experiment.The target gene of miR-146a was analyzed by bioinformatics and double luciferase reporter.The expression levels of target proteins were analyzed by Western blotting.T-test was used for data analysis,with P<0.05 as the difference.Results There were 84 miRNAs differentially expressed in tumor tissues and adjacent tissues,of which miR-146a was the most differentially expressed miRNA.The expression level of miR-146a in signet ring cell carcinoma of stomach(2.96±0.31)was significantly higher than that in adjacent tissues(1.29±0.23,t=3.104,P<0.05).As compared with the control group(1.02±0.19),the expression level of miR-146a in the experimental group(0.33±0.15)was significantly decreased(t=2.864,P<0.05).As compared with the control group[(81.45±8.09)cells],the number of invasive cells in the experimental group[(32.12±4.14)cells]decreased significantly(t=3.173,P<0.05).As compared with the control group[(13.50±3.09)cells],the number of lymp

关 键 词：微小RNA 胃癌 侵袭 转移 

分 类 号：R735.2[医药卫生—肿瘤]