RAC1在宫颈癌组织中的表达及其对宫颈癌细胞上皮-间质转化、迁移、侵袭的影响  

Expression of ras-related C3 botulinum toxin substrate 1(RACl)in cervical cancer(CC)tissues and its effect on epithelial-mesenchymal transition,migration and invasion of CC cells

作　　者：曹玲玲 欧阳云珊 吾米丹·阿不都热合曼 赵倩 杨旺 林晨 CAO Lingling;OUYANG Yunshan;Wumidan Abudureheman;ZHAO Qian;YANG Wang;LIN Chen(Department of Pathology,School of Basic Medical Sciences,Xinjiang Medical University,Xinjiang Key Laboratory of Molecular Biology of Endemic Diseases,Urumqi 830017,China)

机构地区：[1]新疆医科大学基础医学院病理学教研室,新疆地方病分子生物学重点实验室,乌鲁木齐830017

出　　处：《新疆医科大学学报》2025年第2期119-125,共7页Journal of Xinjiang Medical University

基　　金：国家自然科学基金地区基金项目(82060473)。

摘　　要：目的探讨Ras相关的C3肉毒杆菌毒素底物1(RAC1)在宫颈癌组织中的表达及其对宫颈癌细胞上皮-间质转化、迁移、侵袭的影响。方法采用实时荧光定量PCR(qRT-PCR)和免疫组化(IHC)检测宫颈癌组织中的RAC1表达水平,分析其表达与宫颈癌临床病理特征的关系;构建RAC1低表达的慢病毒载体(shRAC1)和空载载体(shNC),选取低表达RAC1的HeLa、SiHa细胞作为shRAC1组,感染空载载体的HeLa、SiHa细胞作为shNC组;采用qRT-PCR检测各组细胞中RAC1 mRNA表达水平;蛋白免疫印迹法检测RAC1、E-Cadherin、N-Cadherin、Vimentin的蛋白表达水平;EdU实验、平板克隆实验检测细胞增殖情况;划痕实验、Transwell检测细胞的迁移和侵袭能力。结果宫颈癌组织中RAC1 mRNA表达水平显著高于癌旁组织(P<0.01)。RAC1表达水平与淋巴结转移和肌层浸润深度有关(P<0.05)。与shNC组相比较,shRAC1组细胞的RAC1 mRNA和蛋白表达水平下降,E-Cadherin表达上调,N-Cadherin和Vimentin表达下调,细胞增殖、迁移和侵袭能力降低,差异具有统计学意义(P<0.05)。结论RAC1在宫颈癌组织和细胞中表达上调,下调其表达可抑制宫颈癌细胞HeLa、SiHa的增殖、上皮-间质转化、迁移和侵袭。RAC1可能成为宫颈癌治疗的潜在靶点。Objective To investigate the expression of RAC1 in cervical cancer(CC)tissues and its effects on epithelial-mesenchymal transition,migration and invasion of CC cells.Methods The expression of RAC1 in CC tissues was assessed using real-time fluorescence quantitative PCR(qRT-PCR)and immunohistochemistry(IHC)and the correlation between RAC1 expression and the clinicopathological characteristics of CC was analyzed.Lentiviral vectors with low expression of RAC1(shRAC1)and control vector(shNC)were constructed,and the low RAC1-expressing HeLa and SiHa cells were selected as shRAC1 group,and HeLa and SiHa cells infected with control vector as shNC group.qRT-PCR was used to detect the expression level of RAC1 mRNA in the cells of each group.Protein immunoblotting was used to detect the protein expression level of RAC1,E-Cadherin,N-Cadherin and Vimentin.EdU assay and plate cloning assay were used to detect cell proliferation.The migration and invasion ability of cells were detected by scratch assay and Transwell.Results The expression level of RAC1 mRNA in CC tissues was significantly elevated compared to that in adjacent non-cancerous tissues(P<0.01),and the level of RAC1 expression was associated with lymph node metastasis and depth of infiltration in the muscularis propria(P<0.05).Compared with shNC group,cells in the shRAC1 group showed decreased levels of RAC1 mRNA and protein expression,up-regulation of E-Cadherin expression,down-regulation of N-Cadherin and Vimentin expression,and decreased cell proliferation,migration and invasion ability,all of which were statistically significant(P<0.05).Conclusion The expression of RAC1 was up-regulated in CC tissues and cells,and down-regulation of its expression could inhibit the proliferation,epithelial-mesenchymal transition,migration and invasion of CC cells HeLa,SiHa.RAC1 may be a potential target for CC treatment.

关 键 词：宫颈癌 上皮-间质转化 RACL 转移 

分 类 号：R737.33[医药卫生—肿瘤]