CEACAM6通过调控上皮间质转化抑制鼻咽癌细胞的增殖和迁移  

CEACAM6 inhibits proliferation and migration of nasopharyngeal carcinoma cells by suppressing epithelial-mesenchymal transition

作　　者：陶露 韦卓利 王月月 项平 TAO Lu;WEI Zhuoli;WANG Yueyue;XIANG Ping(Central Laboratory,First Affiliated Hospital of Bengbu Medical University,Bengbu 233004,China;Department of Anatomy,Bengbu Medical University,Bengbu 233000,China;Anhui Provincial Key Laboratory of Tissue Transplantation,Bengbu 233000,China;Anhui Provincial Key Laboratory of Basic and Translational Research on Inflammation-Related Diseases,Bengbu 233004,China)

机构地区：[1]蚌埠医科大学第一附属医院中心实验室,安徽蚌埠233004 [2]蚌埠医科大学解剖教研室,安徽蚌埠233000 [3]组织移植安徽省重点实验室,安徽蚌埠233000 [4]炎症相关性疾病基础与转化研究安徽省重点实验室,安徽蚌埠233004

出　　处：《南方医科大学学报》2025年第3期566-576,共11页Journal of Southern Medical University

基　　金：安徽省高等学校科学研究项目(2022AH051481);蚌埠医学院自然科学重点项目(2021byzd048);安徽省自然科学基金青年项目(2008085QH404)。

摘　　要：目的明确CEACAM6在鼻咽癌中的表达,探索CEACAM6对鼻咽癌细胞增殖和迁移的影响以及潜在的作用机制。方法通过GEO数据库分析CEACAM6在鼻咽癌中表达情况。TCGA数据库分析CEACAM6在头颈部癌中表达情况以及与生存预期的关系。免疫组织化学技术检测CEACAM6在鼻咽癌组织中的表达情况。构建CEACAM6过表达细胞模型,分为control组(空载)和Lv-CEACAM6组(过表达);CEACAM6敲低细胞模型,分为control组(空载)、sh#1组(敲低)和sh#2组(敲低)。通过CCK-8和Edu染色检测CEACAM6对鼻咽癌细胞增殖的影响。伤口愈合和Transwell检测CEACAM6对鼻咽癌细胞侵袭迁移的影响。鬼笔环肽染色检测CEACAM6对鼻咽癌细胞骨架排列的影响。Western blotting检测CEACAM6对鼻咽癌细胞中FN1、ITGA5、ITGB1、N-cad、Vim和E-cad的蛋白表达影响以及FN1过表达对CEACAM6过表达的鼻咽癌细胞中ITGA5和ITGB1蛋白表达的影响。结果GEO数据库分析表明CEACAM6在鼻咽癌中低表达,TCGA数据库分析表明CEACAM6在头颈部癌中低表达,CEACAM6低表达与预后不良有关。免疫组织化学技术检测结果显示CEACAM6在鼻咽癌组织中低表达。CCK-8和Edu检测结果显示CEACAM6可抑制鼻咽癌细胞的增殖能力(P<0.05)。伤口愈合和Transwell检测结果显示CEACAM6可抑制鼻咽癌细胞侵袭和迁移能力(P<0.05)。鬼笔环肽染色结果显示上调CEACAM6表达后肌动蛋白荧光表达降低。Westen blotting检测结果表明上调CEACAM6表达后FN1、ITGA5、ITGB1下调,E-cad上调,N-cad和Vim下调(P<0.05),FN1过表达可缓解CEACAM6对ITGA5和ITGB1表达的抑制作用(P<0.05)。结论CEACAM6可能通过调控FN1、ITGA5、ITGB1蛋白表达影响上皮间质转化从而抑制鼻咽癌的侵袭和迁移。Objective To investigate CEACAM6 expression in nasopharyngeal carcinoma(NPC)and its regulatory effects on tumor cell proliferation,migration,and epithelial-mesenchymal transition(EMT).Methods CEACAM6 expression in NPC was analyzed using GEO datasets and validated by immunohistochemistry in NPC tissues and by Western blotting and RTqPCR in NPC cell lines(HNE1,C666-1,HK1,5-8F and CNE2Z)and normal nasopharyngeal epithelial NP69 cells.In the NPC cell lines,the effects of lentivirus-mediated CEACAM6 overexpression and knockdown on cell proliferation,migration,invasion and cytoskeletal structures were evaluated using CCK-8 assay,Edu staining,wound healing assay,Transwell assay,and phalloidin staining.Western blotting was performed to determine the expressions of EMT-related proteins(FN1,ITGA5,ITGB1,E-cadherin,N-cadherin and vimentin)in the NPC cells and the effect of FN1 overexpression on ITGA5 and ITGB1 protein expressions.Results Analysis of the data from the GEO datasets suggested that CEACAM6 was significantly downregulated in NPC,which was associated with poor patient prognosis.Immunohistochemistry also showed low expressions of CEACAM6 in clinical NPC tissues(P<0.05).In NPC cells,CEACAM6 overexpression significantly suppressed cell proliferation,migration and invasion and reduced the fluorescence intensity of actin.CEACAM6 overexpression also resulted in significant downregulation of FN1,ITGA5,ITGB1,N-cadherin and vimentin expressions and upregulation of Ecadherin expression,and FN1 overexpression obviously attenuated the inhibitory effect of CEACAM6 overexpression on ITGA5 and ITGB1 expressions.Conclusion CEACAM6 inhibits NPC cell migration and invasion by inhibiting EMT via regulating FN1,ITGA5 and ITGB1 expressions.

关 键 词：CEACAM6 鼻咽癌 迁移 上皮间质转化 

分 类 号：R739.63[医药卫生—肿瘤]