LINC00662通过miR-615-5p/wnt/β-catenin通路调控胃癌细胞增殖、迁移和侵袭  

LINC00662 regulates gastric cancer cell proliferation,migration,and invasion via the miR-615-5p/Wnt/β-catenin pathway

作　　者：孙兵 王超雄 黄坚 方军 Bing Sun;Chao-Xiong Wang;Jian Huang;Jun Fang(Department of Surgery,Jinhua Hospital of Traditional Chinese Medicine,Jinhua 321017,Zhejiang Province,China)

机构地区：[1]金华中医医院外二科,浙江省金华市321017

出　　处：《世界华人消化杂志》2024年第8期600-607,共8页World Chinese Journal of Digestology

摘　　要：背景先前的研究已经表明长链非编码RNAs(long non-coding RNAs,lncRNAs)在包括胃癌在内的多种癌症进展中的重要调节因子的作用.然而,LINC00662的生物学功能及其调控结胃癌进展的潜在机制尚不清楚.目的探讨LINC00662能否靶向miR-615-5p调控胃癌细胞增殖、迁移和侵袭.方法体外培养人胃上皮细胞GES1和胃癌细胞系(SNU-1、AGS和HS-746T),RT-qPCR法检测LINC00662和miR-615-5p表达.SNU-1细胞转染LINC00662小干扰RNA、miR-615-5p模拟物或抑制剂;CCK-8、克隆形成、Transwell分析细胞增殖、迁移和侵袭,蛋白质印迹法检测细胞中基质金属蛋白酶(matrix metalloproteinase,MMP)-2、MMP-9和β-连环蛋白(β-catenin)蛋白表达.双荧光素酶报告实验验证互作关系.结果与GES1细胞比较,胃癌细胞系中LINC00662表达上调而miR-615-5p表达下调(P<0.05).下调LINC00662或上调miR-615-5p后,SNU-1细胞A值、克隆数、迁移数、侵袭数、MMP2、MMP9蛋白表达下调(P<0.05).同时,下调LINC00662降低β-catenin蛋白表达(P<0.05).LINC00662靶向结合miR-615-5p,且下调LINC00662的SNU-1细胞中miR-615-5p表达升高(P<0.05).miR-615-5p抑制剂逆转下调LINC00662对SNU-1细胞增殖、迁移和侵袭的影响.结论LINC00662通过靶向miR-615-5p和激活wnt/β-catenin通路来加速胃癌细胞增殖、迁移和侵袭.BACKGROUND Previous studies have shown the role of long non-coding RNAs(lncRNAs)as important regulators in the progression of various cancers,including gastric cancer.However,the biological function of LINC00662 and the mechanism underlying its regulation of gastric cancer progression are still unclear.AIM To investigate whether LINC00662 can target miR-615-5p to regulate gastric cancer cell proliferation,migration,and invasion.METHODS Human gastric epithelial cells(GES1)and gastric cancer cell lines(SNU-1,AGS,and HS-746T)were cultured in vitro,and the expression levels of LINC00662 and miR-615-5p in these cell types were detected by RT-qPCR.SNU-1 cells were transfected with LINC00662 small interfering RNA,or miR-615-5p mimic or inhibitor,and cell proliferation,migration,and invasion were evaluated by CCK-8,clone formation,and Transwell assays.Western blot analysis was performed to examine the protein expression of matrix metalloproteinase(MMP)-2,MMP-9,andβ-catenin.Dual-luciferase reporter experiment was used to verify the regulatory relationship between LINC00662 and miR-615-5p.RESULTS Compared with GES1 cells,LINC00662 was up-regulated and miR-615-5p was down-regulated in gastric cancer cell lines(P<0.05).After down-regulating LINC00662 or up-regulating miR-615-5p,cell proliferation,migration,and invasion,and MMP2 and MMP9 protein levels in SNU-1 cells were decreased(P<0.05).β-catenin protein level in SNU-1 cells with down-regulated LINC00662 expression was decreased(P<0.05).LINC00662 targets miR-615-5p,and miR-615-5p expression was increased by LINC00662 down-regulation(P<0.05).miR-615-5p inhibitor reversed the effect of down-regulating LINC00662 on SNU-1 cell proliferation,CONCLUSION LINC00662 promotes gastric cancer cell proliferation,migration,and invasion by targeting miR-615-5p and activating the Wnt/β-catenin pathway.

关 键 词：胃癌 LINC00662 miR-615-5p 细胞增殖 侵袭 

分 类 号：R735.2[医药卫生—肿瘤]