miR-425-5p靶向ZNF423基因调控Notch信号通路促进胃癌细胞侵袭转移  

miR-425-5p promotes invasion and metastasis of gastric cancer cells via Notch signal pathway by targeting ZNF423

作　　者：贺爱军[1] 任羽[1] 曹波[1] 李小宝[1] HE Ai-jun;REN Yu;CAO Bo;LI Xiao-bao(Department of Gastrointestinal Surgery,Affiliated Hospital of Yan′an University,Shaanxi Province 716000)

机构地区：[1]陕西省延安大学附属医院胃肠外科,716000

出　　处：《现代消化及介入诊疗》2020年第6期735-739,共5页Modern Interventional Diagnosis and Treatment in Gastroenterology

基　　金：国家自然科学基金项目(81300196);延安市科学技术研究发展计划项目(2013-ku06)。

摘　　要：目的探究miR-425-5p靶向ZNF423基因通过Notch信号通路对胃癌细胞侵袭转移的影响和机制。方法qRT-PCR和Western blot检测人胃上皮细胞GES-1和3种胃癌细胞(AGS、SGC-7901和BGC-823)中miR-425-5p和ZNF423的表达水平。以SGC-7901细胞为研究对象,构建抑制miR-425-5p表达的细胞株,qRT-PCR检测miR-425-5p的表达水平,Transwell实验检测细胞的迁移和侵袭能力,Western blot检测迁移侵袭和Notch信号通路相关蛋白的表达水平。双荧光素酶报告基因实验和Western blot验证miR-425-5p和ZNF423的靶向调控关系。结果与GES-1细胞相比,3种胃癌细胞中miR-425-5p的表达显著上调,ZNF423的表达显著下调。稳定抑制miR-425-5p表达的细胞株构建成功。抑制miR-425-5p可显著抑制MMP-2、MMP-9、Notch1、Hes5和Hey1蛋白的表达,抑制SGC-7901细胞的迁移和侵袭。沉默ZNF423可逆转抑制miR-425-5p表达对胃癌细胞迁移和侵袭的抑制作用。沉默ZNF423还可逆转抑制miR-452-5p表达对胃癌细胞中Notch信号通路的抑制作用。结论miR-425-5p通过下调ZNF423表达激活Notch信号通路,进而促进胃癌细胞的侵袭和转移。Objective To investigate the effect of miR-425-5p on the invasion and metastasis of gastric cancer cells via Notch signaling pathway by targeting ZNF423.Methods The expression levels of miR-425-5p and ZNF423 in human gastric epithelial cells GES-1 and three gastric cancer cells(AGS,SGC-7901 and BGC-823)were detected by qRT-PCR and Western blot.SGC-7901 cells were selected for the subsequently study.SGC-7901 cell line with the inhibition of miR-425-5p was constructed,qRT-PCR was used to detect the expression level of miR-425-5p,Transwell assay was used to detect the cell migration and invasion ability,Western blot was used to detect the expression levels of migration-invasive and Notch signaling pathway-associated proteins.The dual luciferase reporter gene assay and Western blot were used to verify the targeted regulatory relationship between miR-425-5p and ZNF423.Results Compared with GES-1 cells,the expression of miR-425-5p was significantly up-regulated in three gastric cancer cells,while the expression of ZNF423 was significantly down-regulated.The Cell line stably inhibiting the expression of miR-425-5p were successfully constructed.The inhibition of miR-425-5p significantly inhibited the expression of MMP-2,MMP-9,Notch1,Hes5 and Hey1 proteins,and alsoinhibited the migration and invasion of SGC-7901 cells.Silencing ZNF423 reversed the inhibitory effect of anti-miR-425-5p on migration and invasion of gastric cancer cells.Silencing ZNF423 also reversed the inhibitory effect of miR-452-5p expression on Notch signaling pathway in gastric cancer cells.Conclusion miR-425-5p activates the Notch signaling pathway by down-regulating ZNF423,thereby promoting the invasion and metastasis of gastric cancer cells.

关 键 词：miR-425-5p ZNF423 NOTCH信号通路 胃癌 侵袭转移 

分 类 号：R735.2[医药卫生—肿瘤] R573[医药卫生—临床医学]