LEF1-AS1通过Wnt/β-catenin信号通路对胃癌细胞迁移侵袭的影响

Effects of LEF1-AS1 on migration and invasion of gastric cancer cells through Wnt/β-catenin signaling pathway

目的探讨淋巴增强结合因子1反义RNA 1(LEF1-AS1)通过调控Wnt/β-连环蛋白(β-catenin)信号通路对胃癌细胞增殖、迁移和侵袭的影响。方法实时荧光定量PCR(qPCR)检测胃癌细胞和正常胃黏膜细胞GES-1中LEF1-AS1的表达情况。BGC-823细胞分为阴性对照组、LEF1-AS1干扰组和LEF1-AS1干扰+Wnt激动剂组。CCK-8法检测细胞活力,划痕实验和Transwell实验检测细胞迁移和侵袭能力;qPCR和Western blot检测Wnt1、β-catenin和Survivin表达。结果LEF1-AS1在胃癌细胞中的相对表达量高于GES-1细胞(P<0.05)。与阴性对照组比较,LEF1-AS1干扰组BGC-823细胞的增殖和迁移侵袭能力均下降(P<0.05)。LEF1-AS1干扰组Wnt1和β-catenin表达水平低于阴性对照组(P<0.05)。LEF1-AS1干扰+Wnt激动剂组BGC-823细胞的增殖和迁移侵袭能力均强于LEF1-AS1干扰组(P<0.05),且β-catenin和Survivin水平较LEF1-AS1干扰组升高(P<0.05)。结论LEF1-AS1沉默通过抑制Wnt/β-catenin信号通路活化来负调控胃癌细胞的生物学行为,该因子有作为胃癌治疗靶点的潜能。

Objective To investigate the influence of lymphoid enhancer-binding factor 1 antisense RNA 1(LEF1-AS1)on the proliferation,migration and invasion processes of gastric cancer cells through Wnt/β-catenin signaling pathway.Methods Expression patterns of LEF1-AS1 in gastric cancer cell lines and human gastric epithelial cell GES-1 were accessed by real time-quantitative polymerase chain reaction(qPCR).BGC-823 cells were divided into Negative control(NC)group,LEF1-AS1 interference(si-LEF1-AS1)group and si-LEF1-AS1+Wnt activator group.The CCK-8 kit was applied to detect cell viability.The wound healing and Transwell assays were employed to test the migration and invasion abilities of cells.Moreover,qPCR and Western blot were applied to detect the expressions of Wnt1,β-catenin and Survivin.Results LEF1-AS1 were remarkably upregulated in gastric cancer cell lines compared to GES-1 cell(P<0.05).Compared with NC group,the abilities of proliferation,migration and invasion of BGC-823 cells were declined in si-LEF1-AS1 group(P<0.05).Expression levels of Wnt1 andβ-catenin in si-LEF1-AS1 group were decreased as compared with NC group(P<0.05).In addition,the abilities of proliferation,migration and invasion of BGC-823 cells in si-LEF1-AS1+Wnt activator group were enhanced as compared with si-LEF1-AS1 group(P<0.05).Expression levels ofβ-catenin and Survivin in si-LEF1-AS1+Wnt activator group were increased as compared with si-LEF1-AS1group(P<0.05).Conclusion LEF1-AS1 silencing negatively regulates the biological behavior of gastric cancer cells via inhibiting Wnt/β-catenin signaling pathway activation.It has potential as a therapeutic target for gastric cancer.