lncRNA XIST通过调控miR-337-3p/HOXC8轴促进胃癌的发展进程  

lnc RNA XIST promotes gastric cancer progression via regulating mi R-337-3p/HOXC8 axis

作　　者：徐龙健[1] 高建超[1] 郑景珍[1] 赵志娟 钟轩[1] 孙敬国[1] 李东坤[1] XU Longjian;GAO Jianchao;ZHENG Jingzhen;ZHAO Zhijuan;ZHONG Xuan;SUN Jingguo;LI Dongkun(Department of General Surgery,Kailuan General Hospital of Tangshan City,Tangshan 063000,Hebei,China)

机构地区：[1]唐山市开滦总医院普通外科

出　　处：《中国肿瘤生物治疗杂志》2019年第10期1134-1141,共8页Chinese Journal of Cancer Biotherapy

摘　　要：目的:探讨lncRNA XIST(XIST)通过调控miR-337-3p/HOXC8分子轴介导胃癌发展进程的分子机制。方法:选取2013年3月至2018年1月河北省唐山市开滦总医院普通外科手术切除的58例胃癌组织和对应的癌旁组织标本,以及人胃癌细胞系AGS、MGC803、HGC27和人胃黏膜细胞GES-1,用qPCR检测胃癌组织和细胞系中XIST和miR-337-3p的表达水平。将XIST敲降载体、miR-337-3p mimics/inhibitor和HOXC8过表达载体转染进AGS细胞,用CCK-8、Transwell实验检测AGS细胞的增殖及侵袭能力,用WB检测HOXC8及上皮钙黏蛋白(E-cadherin)、神经钙黏蛋白(N-cadherin)和波形蛋白(vimentin)的表达水平。用双荧光素酶报告基因验证XIST、miR-337-3p和HOXC8的靶向关系。结果:XIST在胃癌组织和细胞系中高表达(均P<0.01)。敲降XIST显著抑制AGS细胞的增殖、侵袭和EMT(P<0.05或P<0.01)。XIST靶向作用miR-337-3p并下调其表达,HOXC8是miR-337-3p的靶基因。敲降XIST通过靶向上调miR-337-3p对HOXC8表达的抑制作用,从而抑制AGS细胞增殖、侵袭和EMT(P<0.05或P<0.01)。结论:敲降XIST可抑制AGS细胞增殖、侵袭和EMT,其作用机制是通过靶向miR-337-3p并下调HOXC8的表达。Objective:To investigate the mechanism of lncRNA XIST(XIST)on modulating gastric cancer progression via regulating miR-337-3p/HOXC8 axis.Methods:A total of 58 cases of gastric cancer tissues and corresponding para-cancerous tissues resected from March 2013 to January 2018 in Department of General Surgery,Kailuan General Hospital of Tangshan City were collected for this study;in addition,human gastric cancer cell lines(AGS,MGC803,HGC27)and human gastric mucosal GES-1 cells were also collected.qPCR was used to detect the expressions of XIST and miR-337-3p in above mentioned gastric tissues and cell lines.XIST-knockdown vectors,miR-337-3p mimics,miR-337-3p inhibitor and HOXC8-overexpression vectors were transfected into AGS cells.The proliferation and invasion of AGS cells were detected by CCK-8 and Transwell experiments respectively,and the expression levels of HOXC8,E-cadherin,N-cadherin and vimentin were detected by WB.The targeting relationships between XIST,miR-337-3p and HOXC8 were verified by dual-luciferase reporter gene assay.Results:XIST was up-regulated in gastric cancer tissues and cell lines(all P<0.01).XIST knockdown significantly inhibited proliferation,invasion and EMT of AGS cells(P<0.05 or P<0.01).Moreover,XIST directly interacted with miR-337-3p and down-regulated its expression,while HOXC8 was the target gene of miR-337-3p.Furthermore,XIST knockdown suppressed proliferation,invasion and EMT of AGS cells through up-regulating the inhibitory effect of miR-337-3p on HOXC8(P<0.05 or P<0.01).Conclusion:XIST knockdown can suppress the proliferation,invasion and EMT of AGS cells,which may be related with down-regulation of HOXC8 by targeting miR-337-3p.

关 键 词：胃癌 AGS细胞 增殖 上皮间质转化 lncRNAXIST miR-337-3p HOXC8 

分 类 号：R730.4[医药卫生—肿瘤] R735.2[医药卫生—临床医学]