miR-195靶向FOXK1介导Wnt/β-catenin信号通路调控胃癌细胞侵袭转移的分子机制  

Molecular mechanism of miR-195 targeting FOXK1 mediated Wnt/β-catenin signaling pathway of regulating invasion and metastasis in gastric cancer cells

作　　者：范晓彬 李晓青 宋峰峰 王强[3] FAN Xiao-bin;LI Xiao-qing;SONG Feng-feng;WANG Qiang(Department of Gastrointestinal Surgery,Xingtai Third Hospital,Xingtai 054000,Hebei,China;Department of General Surgery,Binzhou People’s Hospital,Binzhou 256600,Shandong,China;Department of General Surgery,Suining Central Hospital,Suining 629000,Sichuan,China)

机构地区：[1]邢台市第三医院胃肠外科,河北邢台054000 [2]滨州市人民医院普外二科,山东滨州256600 [3]遂宁市中心医院普通外科,四川遂宁629000

出　　处：《生物医学工程与临床》2023年第2期206-211,共6页Biomedical Engineering and Clinical Medicine

基　　金：邢台市重点研发计划项目(2020ZC232)。

摘　　要：目的探究微小RNA(miR)-195靶向叉头盒蛋白K1(FOXK1)介导Wnt/β-catenin信号通路调控胃癌细胞侵袭转移的分子机制。方法选择140例胃癌组织和癌旁正常组织,其中男性77例,女性63例;年龄46~73岁,平均年龄55.34岁(标准差3.68岁)。检测其中miR-195、FOXK1和β-catenin的表达水平。通过Pearson检验分析相关性。通过双荧光素酶报告验证miR-195与FOXK1的相关性。将人胃癌细胞分为4组:对照组、miR-195组、FOXK1组和miR-195+FOXK1组。通过转染miR-195类似物和/或FOXK1质粒来提高miR-195和/或FOXK1的水平。检测各组细胞增殖、侵袭能力,以及β-catenin转录和蛋白表达水平。结果胃癌组织中miR-195水平显著低于正常组织,而FOXK1和β-catenin表达水平显著高于正常组织(P<0.05)。FOXK1与β-catenin正相关,miR-195分别与FOXK1和β-catenin负相关(P<0.05)。验证结果显示miR-195与FOXK1的靶向结合(P<0.05)。miR-195组FOXK1蛋白、增殖、侵袭、β-catenin mRNA和蛋白水平显著低于对照组(P<0.05)。FOXK1组FOXK1蛋白、增殖、侵袭、β-catenin mRNA和蛋白水平显著高于对照组(P<0.05)。miR-195+FOXK1组FOXK1蛋白、增殖、侵袭、β-catenin mRNA和蛋白水平高于miR-195组并低于FOXK1组(P<0.05)。结论miR-195可通过靶向FOXK1抑制Wnt/β-catenin通路,抑制胃癌细胞的侵袭和转移。Objective To explore the molecular mechanism of microRNA( miR)-195 targeting forkhead box protein K1(FOXK1)-mediated Wnt/β-catenin signaling pathway in regulating invasion and metastasis of gastric cancer cells. Methods A total of 140 cases of gastric cancer tissues and adjacent normal tissues were enrolled, which included 77 males and 63females, aged 46-73 years old with mean age of 55.34 years old(standard deviation 3.68 years old). The expression levels of miR-195, FOXK1 and β-catenin were detected. The correlation was analyzed by Pearson test. The correlation between miR-195 and FOXK1 was verified by dual luciferase. The gastric cancer cells were divided into 4 groups: control group, miR-195group, FOXK1 group and miR-195 + FOXK1 group. The levels of miR-195 and/or FOXK1 were increased by transfection of miR-195 analogues and/or FOXK1 plasmids. The cell proliferation, invasion ability, and β-catenin transcription and protein expression levels were detected in each group. Results The level of miR-195 in gastric cancer tissues was significantly lower than that of normal tissues, while expression levels of FOXK1 and β-catenin were significantly higher than those of normal tissues(P < 0.05). FOXK1 was positively correlated with β-catenin, and miR-195 was negatively correlated with FOXK1 andβ-catenin(P < 0.05). The verification results showed the targeted binding of miR-195 and FOXK1(P < 0.05). The FOXK1protein, proliferation, invasion, β-catenin mRNA and protein levels in miR-195 group were significantly lower than those in control group(P < 0.05). FOXK1 protein, proliferation, invasion, β-catenin mRNA and protein levels in FOXK1 group were significantly higher than those in control group( P < 0.05). The levels of FOXK1 protein, proliferation, invasion, β-catenin mRNA and protein in miR-195 + FOXK1 group were higher than those in miR-195 group and lower than those in FOXK1group(P < 0.05). Conclusion It is demonstrated that miR-195 could inhibit Wnt/β-catenin pathway by targeting FOXK1, and inhibit invasi

关 键 词：胃癌 微小RNA-195(miR-195) FOXK1 WNT/Β-CATENIN 细胞侵袭 细胞转移 

分 类 号：R735.2[医药卫生—肿瘤] Q75[医药卫生—临床医学]