LINC01426调控胃癌细胞增殖、迁移及侵袭的分子机制研究  

Molecular mechanism for LINC01426 to regulate gastric cancer cell proliferation,migration,and invasion

作　　者：刘栋[1] 夏阿东 李松 张凯[1] 陈丹[2] Dong Liu;A-Dong Xia;Song Li;Kai Zhang;Dan Chen(Department of Hepatobiliary Surgery,Jinhua People’s Hospital,Jinhua 321000,Zhejiang Province,China;Department of Gastroenterology,Jinhua People’s Hospital,Jinhua 321000,Zhejiang Province,China)

机构地区：[1]金华市人民医院肝胆外科,浙江省金华市321000 [2]金华市人民医院消化内科,浙江省金华市321000

出　　处：《世界华人消化杂志》2022年第8期356-363,共8页World Chinese Journal of Digestology

基　　金：金华市科学技术局公益类课题项目,No.2018-4-049.

摘　　要：背景胃癌发病机制复杂,其中癌基因和抑癌基因表达失调是其进展的关键因素.miR-153-5p已被证实在肝癌中具有抑癌作用,lncRNA位于细胞周期激酶抑制因子4(INK4)基因座中反义RNA(ANRIL)促进肝癌细胞迁移.但LINC01426是否靶向miR-153-5p参与胃癌进展仍有待研究.目的探讨长基因间非编码RNA 01426(LINC01426)是否靶向miR-153-5p影响胃癌细胞的增殖、迁移和侵袭.方法实时定量PCR(RT-qPCR)分析LINC01426和miR-153-5p在胃癌组织、癌旁组织、胃癌细胞系(SNU-1、AGS、HS-746T)和正常胃上皮细胞(GES1)中表达量.Pearson相关性分析胃癌组织中LINC01426和miR-153-5p表达的相关性.生物信息学在线分析、双荧光素酶报告实验、RT-qPCR分析和证实LINC01426对miR-153-5p调控作用.噻唑蓝(methylthiazolyldiphenyl-tetrazolium bromide,MTT)实验、Transwell实验分析LINC01426和miR-153-5p表达对SNU-1细胞增殖、迁移和侵袭的影响.结果胃癌组织、细胞中LINC01426表达量显著高于癌旁组织和GES1细胞(P<0.05),miR-153-5p表达量显著高于癌旁组织和GES1细胞(P<0.05).Pearson相关性分析结果显示,胃癌组织中LINC01426和miR-153-5p的表达呈负相关(r=-0.828,P<0.05).LINC01426靶向结合并负调控miR-153-5p.抑制LINC01426表达或过表达miR-153-5p显著降低SNU-1细胞活力、迁移和侵袭能力(P<0.05),而抑制miR-153-5p表达显著升高SNU-1细胞活力、迁移和侵袭能力(P<0.05).抑制miR-153-5p表达显著逆转LINC01426抑制对SNU-1细胞活力、迁移和侵袭的影响(P<0.05).结论抑制LINC01426可阻碍胃癌细胞增殖、侵袭和迁移,这与LINC01426负调控miR-153-5p有关.BACKGROUND The pathogenesis of gastric cancer is complex,among which the dysregulation of expression of oncogenes and tumor suppressor genes is a key factor.MiR-153-5p has been confirmed to have a tumor suppressor effect in liver cancer,and antisense noncoding RNA in the INK4 locus(ANRIL)can promote liver cancer cell migration.However,whether long intergenic non-coding RNA 01426(LINC01426)targets miR-153-5p and participates in the progression of gastric cancer remains to be studied.AIM To investigate whether LINC01426 targets miR-153-5p to affect the proliferation,migration,and invasion of gastric cancer cells.METHODS Real-time quantitative PCR(RT-qPCR)was used to analyze the expression of LINC01426 and miR-153-5p in gastric cancer tissues,tumor adjacent tissues,gastric cancer cell lines(SNU-1,AGS,and HS-746T),and normal gastric epithelial cells(GES1).The correlation of LINC01426 and miR-153-5p expression in gastric cancer tissues was analyzed by Pearson correlation.Online bioinformatics analysis,dual luciferase reporter assay,and RT-qPCR were applied to confirm the regulatory effect of LINC01426 on miR-153-5p.The effect of LINC01426 and miR-153-5p expression on cell viability,migration,and invasion was evaluated by MTT and transwell assays.RESULTS LINC01426 was highly expressed in gastric cancer tissue and cells compared with tumor adjacent tissue and GES1 cells(P<0.05),but miR-153-5 was lowly expressed in gastric cancer tissue and cells(P<0.05).Pearson correlation analysis showed that the expression of LINC01426 and miR-153-5p in gastric cancer tissues was negatively correlated(r=-0.828,P<0.05).LINC01426 could target and negatively regulate miR-153-5p.LINC01426 inhibition or miR-153-5p overexpression remarkably reduced the proliferation,migration,and invasion of SNU-1 cells(P<0.05),while miR-153-5p inhibition had opposite effects(P<0.05).The effects of LINC01426 inhibition on the proliferation,migration,and invasion of SNU-1 cells were significantly reversed by inhibiting miR-153-5p(P<0.05).CONCLUSION Inhibitio

关 键 词：LINC01426 miR-153-5p 胃癌 细胞增殖 迁移 侵袭 

分 类 号：R735.2[医药卫生—肿瘤]