lncRNA SNHG1结合miR-145促进胃癌细胞增殖的机制研究  

LncRNA SNHG1 promoting the growth of gastric cancer through binding to miR-145

作　　者：周锋利[1] 褚以忞[1] 李吉[1] 杨大明[1] 彭海霞[1] 徐莹[1] ZHOU Fengli;CHU Yimin;LI Ji;YANG Daming;PENG Haixia;XU Ying(Digestive Endoscopy Center,Tongren Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200336,China)

机构地区：[1]上海交通大学医学院附属同仁医院内窥镜室,上海200336

出　　处：《检验医学》2020年第10期1062-1069,共8页Laboratory Medicine

基　　金：上海市卫生和计划生育委员会青年科研项目(20174Y0084)。

摘　　要：目的探讨小核仁RNA宿主基因1(SNHG1)作为竞争性内源RNA(ceRNA)竞争性结合微小RNA-145(miR-145),从而促进胃癌细胞生长的机制。方法利用Kaplan-Meier Plotter网站分析SNHG1与胃癌生存期的相关性;生物信息分析和实时荧光定量聚合酶链反应(qRT-PCR)检测SNHG1在胃癌及癌旁组织中的表达及SNHG1与miR-145表达的关系;CCK8实验检测过表达及敲低SNHG1对胃癌细胞生长情况的影响;荧光素酶报告基因实验检测SNHG1与miR-145的结合情况;分别及同时上调SNHG1、miR-145后采用免疫印迹法检测β-连环蛋白(CTNNB1)、骨髓瘤病毒原癌基因(MYC)蛋白表达的变化。结果在胃癌患者中,SNHG1表达水平低者较高者总生存期延长(P=0.015)。胃癌组织SNHG1表达明显升高(P<0.05)。过表达SNHG1可以促进胃癌细胞增殖,敲低SNHG1可抑制细胞增殖;荧光素酶报告基因实验结果显示,SNHG1和miR-145能有效结合;体外实验表明,miR-145下调CTNNB1、MYC蛋白表达,SNHG1促进CTNNB1、MYC蛋白表达,且SNHG1能抑制miR-145下调CTNNB1和MYC蛋白。结论SNHG1在胃癌组织中高表达,且通过结合miR-145上调CTNNB1、MYC蛋白表达,促进胃癌细胞生长,是参与胃癌生物学行为的机制之一。Objective To investigate small nucleolar RNA host gene 1(SNHG1)promoting the growth of gastric cancer through binding to microRNA-145(miR-145).Methods Kaplan-Meier Plotter database analyzed the correlation of SNHG1 with gastric cancer overall survival.Bioinformatics analysis and real-time fluorescence quantitation polymerase chain reaction(qRT-PCR)were used to investigate the expression level and the expression relationship of SNHG1 and miR-145 in gastric cancer.The influence of overexpression and knock-down of SNHG1 on the growth of gastric cancer cell was determined by CCK8 assay.Luciferase reporter gene assay studied the interaction between SNHG1 and miR-145.Western blot was used to determined the change of CTNNB1 and MYC protein with the transfection of SNHG1,miR-145 and SNHG1 with miR-145.Results The overall survival of patients with low SNHG1 expression was longer than that of patients with high SNHG1 expression(P=0.015).Compared to adjacent tissues,the expression level of SNHG1 in gastric cancer tissues was increased(P<0.05).The overexpression of SNHG1 promoted the growth of gastric cancer cells,while knock-down SNHG1 inhibited cell growth.Luciferase reporter assay showed that SNHG1 could bind to miR-145 effectively.The miR-145 down-regulated the expressions of CTNNB1 and MYC proteins,SNHG1 promoted the expressions of CTNNB1 and MYC proteins,and SNHG1 inhibited the down-regulation of CTNNB1 and MYC proteins by miR-145.Conclusions The over-expressed SNHG1 in gastric cancer binding to miR-145 enhances the expression of CTNNB1 and MYC proteins that could promote gastric cancer growth.

关 键 词：小核仁RNA宿主基因1 微小RNA-145 细胞生长 胃癌 

分 类 号：R446.7[医药卫生—诊断学]