临床外科杂志 ›› 2025, Vol. 33 ›› Issue (9): 974-980.doi: 10.3969/j.issn.1005-6483.20241040

• 论著 • 上一篇    下一篇

LncRNA MAGI2-AS3调节miR-194-5p/CAV1轴对胃癌细胞迁移、侵袭和上皮间质转化的影响

李广鑫 权慧娟 高志娟 王肖君 李良 曹玉庆 刘东生   

  1. 056002 河北邯郸,邯郸市第一医院普外五科(李广鑫、高志娟、曹玉庆、刘东生),心内二科(权慧娟), 肝胆外一科(王肖君),心脏大血管外一科 (李良)
  • 收稿日期:2024-06-27 出版日期:2025-10-16 发布日期:2025-10-16
  • 通讯作者: 刘东生,Email:n06icc@163.com
  • 基金资助:
    邯郸市科学技术研究与发展计划项目(23422083024ZC)

Effects of LncRNA MAGI2-AS3 on the migration,invasion,and epithelial mesenchymal transition of gastric cancer cells by regulating the miR-194-5p/CAV1 axis

LI Guangxin*,QUAN Huijuan,GAO Zhijuan,WANG Xiaojun,LI Liang,CAO Yuqing,LIU Dongsheng   

  1. *Department of General Surgery,the First Hospital of Handan City,Handan 056002,China
  • Received:2024-06-27 Online:2025-09-20 Published:2025-10-16

摘要: 目的 探讨长链非编码RNA MAGI2反义链RNA3(lncRNA MAGI2-AS3)调节miR-194-5p/小窝蛋白-1(CAV1)轴对胃癌(GCa)细胞迁移、侵袭和上皮间质转化(EMT)的影响。方法 2022年8月~2023年12月行手术切除的GCa病人52例,收集癌组织及癌旁组织标本,体外培养AGS、MKN45、HGC-27、GES1细胞,qRT-PCR检测组织样本及细胞系中MAGI2-AS3、miR-194-5p和CAV1表达。将AGS细胞分为AGS组,sh-AGS组,sh-MAGI2-AS3组,miR-NC组,in-miR-194-5p组。比较各组细胞增殖、凋亡、迁移和侵袭情况。免疫印迹法分析各组细胞钙黏蛋白E(E-cadherin)、CAV1、增殖细胞核抗原(PCNA)、钙黏蛋白N(N-cadherin)、Bax、基质金属蛋白酶2(MMP2)、波形蛋白(vimentin)表达。双荧光素酶实验分析MAGI2-AS3与miR-194-5p、miR-194-5p与CAV1间的关系。结果 GCa组织中MAGI2-AS3 mRNA表达、CAV1 mRNA表达和CAV1蛋白阳性表达率升高,miR-194-5p mRNA表达降低(P<0.05)。HGC-27、MKN45、AGS细胞中MAGI2-AS3 mRNA表达、CAV1 mRNA表达和CAV1蛋白表达较GES1细胞增加,miR-194-5p mRNA表达较GES1细胞降低(P<0.05)。与AGS组和sh-AGS组比较,sh-MAGI2-AS3组细胞吸光度、克隆数、侵袭和迁移数、CAV1、PCNA、N-cadherin、MMP2、vimentin表达降低,凋亡率、E-cadherin、Bax表达升高,差异有统计学意义(P<0.05);与miR-NC组和sh-MAGI2-AS3组比较,in-miR-194-5p组细胞吸光度、克隆数、侵袭和迁移数、CAV1、PCNA、N-cadherin、MMP2、vimentin表达升高,凋亡率、E-cadherin、Bax表达降低(P<0.05)。ENCORI数据库显示,MAGI2-AS3与miR-194-5p、miR-194-5p与CAV1间存在多个结合位点。与WT-MAGI2-AS3+miR-NC组比,WT-MAGI2-AS3+miR-194-5p组荧光素酶活性下降(P<0.05),与WT-CAV1+miR-NC组比,WT-CAV1+miR-194-5p组荧光素酶活性下降(P<0.05)。结论 LncRNA MAGI2-AS3沉默能靶向miR-194-5p下调CAV1,从而抑制GCa细胞迁移、侵袭和EMT。

关键词: 长链非编码RNA MAGI2反义链RNA3;miR-194-5p/小窝蛋白-1轴;胃癌细胞;上皮间质转化

Abstract: Objective To investigate the effects of long non coding RNA MAGI2 antisense chain RNA3 (LncRNA MAGI2-AS3) on the migration,invasion,and epithelial mesenchymal transition (EMT) of gastric cancer (GCa) cells by regulating the miR-194-5p/caveolin-1 (CAV1) axis.Methods Fifty-two GCa patients who underwent surgical resection in our hospital from August 2022 to December 2023 were selected.Cancer and adjacent tissues were collected,and AGS,MKN45,HGC-27,and GES1 cells were cultured in vitro.The expression of MAGI2-AS3,miR-194-5p,and CAV1 in tissue samples and cell lines was analyzed.AGS cells were randomly separated into AGS group,sh-AGS group sh-MAGI2-AS3 group,miR-NC group,and in miR-194-5p group.The proliferation,apoptosis,migration,and invasion of cells in each group were compared.Immunoblotting was applied to analyze the expression of E-cadherin,CAV1,proliferating cell nuclear antigen (PCNA),N-cadherin,Bax,matrix metalloproteinase 2 (MMP2),and vimentin of cells in each group.Dual luciferase assay was applied to analyze the relationship between MAGI2-AS3 and miR-194-5p,and between miR-194-5p and CAV1.Results The expression of MAGI2-AS3 mRNA,CAV1 mRNA,and positive expression rate of CAV1 protein in GCa tissue increased,while the expression of miR-194-5p mRNA decreased (P<0.05).The expression of MAGI2-AS3 mRNA,CAV1 mRNA,and CAV1 protein in HGC-27,MKN45,and AGS cells was higher than that of GES1 cells,the expression of miR-194-5p mRNA was lower than that of GES1 cells (P<0.05).Compared with the AGS and sh-AGS groups,the cell absorbance,number of clones,invasion and migration,expression of CAV1,PCNA,N-cadherin,MMP2,and vimentin in sh-MAGI2-AS3 group decreased,the apoptosis rate,expression of E-cadherin,and Bax increased (P<0.05).Compared with the miR-NC group and sh-MAGI2-AS3 group,the cell absorbance,number of clones,invasion and migration,expression of CAV1,PCNA,N-cadherin,MMP2,and vimentin in in-miR-194-5p group increased,the apoptosis rate,expression of E-cadherin,and Bax reduced (P<0.05).ENCORI database found that there were multiple binding sites between MAGI2-AS3 and miR-194-5p,and between miR-194-5p and CAV1.Compared with the WT-MAGI2-AS3+miR-NC group,the luciferase activity in the WT-MAGI2-AS3+miR-194-5p group decreased (P<0.05),while compared with the WT-CAV1+miR-NC group,the luciferase activity in the WT-CAV1+miR-194-5p group decreased (P<0.05).Conclusion LncRNA MAGI2-AS3 silencing can target miR-194-5p to downregulate CAV1,thereby inhibiting GCa cell migration,invasion,and EMT.

Key words: long non coding RNA MAGI2 antisense chain RNA3;miR-194-5p/caveolin-1 axis;gastric cancer cells;epithelial mesenchymal transition

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