METTL5对肺腺癌细胞迁移和侵袭的影响及机制  

ROLE OF METTL5 IN MIGRATION AND INVASION OF LUNG ADENOCARCINOMA CELLS AND MECHANISMS

作　　者：彭修法 王蕊红 王晔[2] 刘凤娟[1] 张春玲[1] PENG Xiufa;WANG Ruihong;WANG Ye;LIU Fengjuan;ZHANG Chunling(Department of Respiratory and Critical Care Medicine,The Affiliated Central Hospital of Qingdao University,Qingdao 266042,China)

机构地区：[1]青岛大学附属青岛市中心医院呼吸与危重症医学科,山东青岛266042 [2]青岛大学附属青岛市中心医院检验科,山东青岛2660421

出　　处：《青岛大学学报（医学版）》2023年第5期645-650,共6页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金资助项目(82072927)。

摘　　要：目的探讨甲基转移酶样蛋白5(METTL5)基因对肺腺癌细胞迁移和侵袭功能的影响及潜在机制。方法使用基因表达数据集(GEO)数据库分析肺腺癌及癌旁组织中METTL5的表达差异,采用Western blot方法检测正常肺上皮BEAS-2B与肺腺癌A549、H1975细胞系中METTL5蛋白的表达水平。应用LV3-METTL5-shRNA慢病毒感染肺腺癌A549和H1975细胞系以敲低其METTL5基因表达,Western blot法验证沉默效果。成功敲低METTL5基因后,通过Transwell TM实验检测两种细胞系迁移、侵袭能力,用Western blot法检测上皮间质转化(EMT)标记物E-Cadherin、Vimentin蛋白表达。结果GEO数据库分析结果显示,肺腺癌组织METTL5的表达显著高于癌旁正常组织,且高表达的病人预后更差。METTL5在肺腺癌A549和H1975细胞中表达显著高于正常肺上皮BEAS-2B细胞系。敲低METTL5后A549和H1975细胞的迁移、侵袭能力显著降低,且间质标记物Vimentin表达显著下调,上皮标记物E-Cadherin表达显著上调。结论METTL5可能通过促进EMT过程促进肺腺癌细胞的迁移和侵袭。Objective To investigate the role of the methyltransferase-like protein 5(METTL5)gene in the migration and invasion of lung adenocarcinoma cells and the potential mechanisms.Methods METTL5 expression levels in lung adenocarcinoma and paracancerous tissues were compared through the Gene Expression Omnibus(GEO)database.METTL5 protein expression levels in normal lung epithelial cells(BEAS-2B)and lung adenocarcinoma cell lines(A549 and H1975)were determined by Western blot.A549 and H1975 cell lines were infected with the LV3-METTL5-shRNA lentivirus to knockdown the expression of the METTL5 gene,which was verified by Western blot for the silencing effects.After successfully knocking down the METTL5 gene,transwell assay was used to determine the migration and invasion abilities of the two cell lines.The expression of epithelial-mesenchymal transition markers(E-Cadherin and Vimentin proteins)was measured by Western blot.Results The GEO analysis showed that the expression of METTL5 was significantly higher in lung adenocarcinoma tissues than in paracancerous tissues,and patients with high METTL5 expression had a significantly poorer prognosis.Lung adenocarcinoma A549 and H1975 cell lines had significantly higher METTL5 levels than the normal lung epithelial cell line BEAS-2B.After knocking down METTL5,A549 and H1975 cells showed significantly reduced migration and invasion abilities,significantly down-regulated expression of the mesenchymal marker Vimentin,and significantly up-regulated expression of the epithelial marker E-Cadherin.Conclusion METTL5 can increase the migration and invasion of lung adenocarcinoma cells by promoting the process of epithelial-mesenchymal transition.

关 键 词：肺腺癌 蛋白甲基转移酶类 上皮-间质转化 细胞运动 

分 类 号：R734.2[医药卫生—肿瘤] R329.28[医药卫生—临床医学]