微小RNA在叉头转录因子M_1激活非小细胞肺癌上皮向间质转化中的作用  

The role of microRNAs in activation of epithelial-mesenchymal transition in non-small-cell lung cancer by forkhead box M_1

作　　者：吴艳[1] 邹黎菲[1] 惠复新[1] 汪家坤[1] WU Yan ZOU Li-fei HUI Fu-xin WANG Jia-kun(Department of Respiratory Medicine, Wuxi People’ s Hospital Affiliated to Nanjing Medical University, Wuxi 214023,Jiangsu,China)

机构地区：[1]南京医科大学附属无锡人民医院呼吸科,无锡214023

出　　处：《中国临床医学》2016年第6期739-743,共5页Chinese Journal of Clinical Medicine

摘　　要：目的:探讨微小RNA(microRNA)在叉头转录因子M_1(Fox M_1)激活非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞上皮向间质转化(epithelial-mesenehymal transition,EMT)中的作用。方法:将Fox M_1过表达质粒,Fox M_1-shRNA,miR-539、miR-485-5p模拟物及其抑制物转染至人NSCLC细胞株中,应用Western印迹和real-time PCR检测细胞株中Fox M_1蛋白和mRNA及miR-539、miR-485-5p的表达。同时应用CCK-8和细胞迁移实验观察Fox M_1、miR-539和miR-485-5p对NSCLC细胞的增殖和侵袭功能的影响。应用荧光素酶报告基因实验检测miR-539和miR-485-5p与EMT调控蛋白ZEB_1和Snail_1的关系。结果:Fox M_1过表达下调NSCLC细胞中miR-539、miR-485-5p,转染Fox M_1-shRNA后NSCLC细胞中miR-539、miR-485-5p升高。MiR-539和miR-485-5p抑制Fox M_1对NSCLC细胞增殖和侵袭的促进作用。NSCLC细胞中miR-539对EMT调控蛋白ZEB_1,miR-485-5p对EMT调控蛋白Snail_1的表达有抑制作用。结论:miR-539和miR-485-5p能抑制NSCLC细胞中Fox M_1-EMT通路,从而影响NSCLC细胞的增殖和侵袭,抑制NSCLC的远处转移。Objective ： To investigate the role of microRNAs in Fox Mi-induced non-small cell lung cancer （NSCLC）epithelial-mesenchymal transition （E M T ）. Methods： Over expression Fox Mi plasmid, Fox M i-shRNA, miR-539, miR-485-5p mimics and inhibitor were transfected into NSCLC cells. The expression of Fox Mi protein and mRNA, miR-539 and miR-485-5p were detected by Western blotting and real-time P C R The CCK-8 and cell migration was used to observe the effect ofFox M i, miR-539 and miR-485-5p on the proliferation and invasion of NSCLC. Luciferase reporter assay was used to explorethe relationship between miRNAC miR-539 and miR-485-5p） and EM T regulatory protein （ ZEBi and Snaili）. Results： RealtimeRT-PCR and Western blotting showed Fox Mi over expression inhibited the expression of miR-539, miR-485-5p, miR-539and miR-485-5p in NSCLC cells were increased after transfected Fox Mi-shRNA. MiR-539 and miR-485-5p suppressedenhancement of proliferation and invasion of NSCLC cells by Fox M i. miR-539 targeted and inhibited the translation of Z E B i,miR-485-5p targeted and inhibited the translation of Snaili in NSCLC cells. Conclusions： The mechanism of Fox Mi upregulationof EM T protein is to decrease the expression of miR-539 and miR-485-5p in NSCLC cells？ thus to affect theproliferation and invasion of NSCLC cells and to inhibit distant metastasis.

关 键 词：叉头转录因子M1 上皮向间质转化 非小细胞肺癌 微小RNA 

分 类 号：R734.2[医药卫生—肿瘤]