FGL1调控口腔鳞状细胞癌细胞上皮-间充质转化的机制及其与临床病理特征的关系  

Mechanism of FGL1 regulating epithelial-mesenchymal transition in oral squamous cell carcinoma cells and the relationship with clinicopathological features

作　　者：田丽丽 戴盟 郭红燕 TIAN Lili;DAI Meng;GUO Hongyan(Department of Stomatology,Fourth People’s Hospital of Liaocheng City,Liaocheng Shandong 252000,China)

机构地区：[1]聊城市第四人民医院口腔科,山东聊城252000

出　　处：《临床与病理杂志》2023年第12期2080-2089,共10页Journal of Clinical and Pathological Research

摘　　要：目的:探讨纤维蛋白原样蛋白1(fibrinogen-like protein 1,FGL1)表达与口腔鳞状细胞癌(以下简称“口腔鳞癌”)患者预后的相关性,并分析FGL1对口腔鳞癌细胞增殖、迁移、侵袭和上皮-间充质转化(epithelialmesenchymal transition,EMT)的作用。方法:收集50对口腔鳞癌组织(口腔鳞癌组)和相应的癌旁组织(癌旁组),采用免疫组织化学染色检测FGL1蛋白阳性染色细胞百分比,根据免疫组织化学评分设为FGL1低表达组和FGL1高表达组;采用Kaplan-Meier法和Log-rank检验分析FGL1表达对患者预后的影响;将口腔鳞癌细胞株HSC-4设为干扰小RNA(small interfering RNA,siRNA)阴性对照组(si-Con组)、siRNA FGL1组(si-FGL1组)和共转染si-FGL1+β-连环素组,利用细胞计数试剂盒8(cell counting kit 8,CCK-8)、克隆形成、划痕和Transwell小室实验分别检测HSC-4细胞生长、迁移和侵袭;采用蛋白质印迹法测定HSC-4细胞EMT标志物E-钙黏素、N-钙黏素和细胞核内β-连环素表达水平;采用双荧光素酶报告基因检测FGL1对β-连环素信号活化(TOP/FOP比值)的影响。结果:与癌旁组相比,口腔鳞癌组FGL1蛋白免疫组织化学评分显著升高(P<0.01);与FGL1低表达组相比,FGL1高表达组患者预后更差(P<0.01);与si-Con组相比,si-FGL1组HSC-4细胞增殖、迁移、侵袭及N-钙黏素和细胞核内β-连环素水平均降低,E-钙黏素表达增加(均P<0.01);与si-Con组相比,si-FGL1组HSC-4细胞TOP/FOP比值显著降低(P<0.01);与si-FGL1组相比,siFGL1+β-连环素组HSC-4细胞增殖、迁移、侵袭及N-钙黏素和细胞核内β-连环素水平均升高,E-钙黏素蛋白表达降低(均P<0.01)。结论:FGL1在口腔鳞癌组织中高表达,其高表达与口腔鳞癌患者预后较差相关。FGL1通过调控HSC-4细胞核内β-连环素表达,从而影响口腔鳞癌细胞增殖、迁移、侵袭及EMT。Objective:To investigate the correlation between the expression of fibrinogen-like protein 1(FGL1)and the prognosis of patients with oral squamous cell carcinoma,and to analyze the role of FGL1 in the proliferation,migration,invasion,and epithelial-mesenchymal transformation(EMT)of oral squamous cell carcinoma cells.Methods:A total of 50 pairs of oral squamous cell carcinoma tissues(oral squamous cell carcinoma group)and corresponding adjacent tissues(adjacent group)were collected.Immunohistochemistry(IHC)staining was performed to detect the percentage of FGL1-positive staining cells.According to the IHC score,the patients were divided into a FGL1 low-expression group and a FGL1 high-expression group.Kaplan-Meier method and Logrank test were used to analyze the effect of FGL1 expression on the prognosis of patients.The oral squamous cell carcinoma cell line HSC-4 was divided into a small interfering RNA(siRNA)negative control group(si-Con group),a siRNA FGL1(si-FGL1)group,and a co-transfected si-FGL1+β-catenin group.Cell counting kit-8(CCK-8),colony formation,scratch,and Transwell assay were conducted to detect cell growth,migration,and invasion of the HSC-4 cells.Western blotting was performed to determine the expression levels of EMT markers(E-cadherin,N-cadherin,and nuclearβ-catenin)in HSC-4 cells.The dualluciferase reporter gene assay was used to detect the effect of FGL1 on the activation ofβ-catenin signaling(TOP/FOP ratio).Results:Compared with the adjacent group,the IHC score of FGL1 protein in the oral squamous cell carcinoma group was significantly increased(P<0.01).Patients in the FGL1 high-expression group had a worse prognosis than those in the FGL1 low-expression group(P<0.01).Compared with the si-Con group,HSC-4 cell proliferation,migration,invasion,and levels of N-cadherin and nuclearβ-catenin were decreased,while E-cadherin expression was increased in the si-FGL1 group(all P<0.01).Compared with the si-Con group,the TOP/FOP ratio of HSC-4 cells in the si-FGL1 group was significantly decreased(

关 键 词：纤维蛋白原样蛋白1 口腔鳞状细胞癌 侵袭 迁移 上皮间质转化 Β-连环素 

分 类 号：R739.8[医药卫生—肿瘤]