下调METTL5通过Wnt/β-catenin信号通路抑制三阴乳腺癌细胞增殖、迁移与侵袭  

Down-regulation of METTL5 inhibits proliferation,migration and invasion of triple-negative breast cancer cells through Wnt/β-catenin signaling pathway

作　　者：吴坤琳[1,2] 严乾壹 王德星 缪秀英[2] 张惠灏[1,2] WU Kun-lin;YAN Qian-yi;WANG De-xing;LIAO Xiu-ying;ZHANG Hui-hao(Dept of Thyroid and Breast Surgery,First Affiliated Hospital of Fujian Medical University,National Regional Medical Center of Binhai Hospital,Fuzhou 350005,China;Comprehensive Surgery Zone 2,Binhai Hospital Area,First Affiliated Hospital of Fujian Medical University,National Regional Medical Center of Binhai Hospital,Fuzhou 350005,China;The First Clinical Medical College of Fujian Medical University,Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院甲状腺乳腺外科,福建福州350005 [2]福建医科大学附属第一医院滨海院区国家区域医疗中心综合外科二区,福建福州350005 [3]福建医科大学第一临床医学院,福建福州350005

出　　处：《中国药理学通报》2024年第2期285-291,共7页Chinese Pharmacological Bulletin

基　　金：福建省自然科学基金项目(No 2020J01944,2022J01698)。

摘　　要：目的探讨甲基转移酶5(methyltransferase-like 5,METTL5)在三阴乳腺癌(triple-negative breast cancer,TNBC)中的作用和潜在机制。方法采用免疫组织化学方法和Western blot检测TNBC肿瘤组织和细胞系中METTL5的表达情况。用靶向METTL5的shRNA(shRNA-METTL5)转染TNBC细胞后,用CCK-8、集落形成、伤口愈合以及Transwell实验分别检测细胞增殖活性、迁移与侵袭,Western blot检测Wnt/β-catenin信号关键蛋白的表达。构建异种移植瘤模型,验证敲降METTL5对TNBC细胞在体内生长以及Wnt/β-catenin信号活性的影响。结果METTL5在TNBC肿瘤组织和细胞系中表达上调(P<0.01)。敲降METTL5可抑制TNBC细胞的增殖、迁移和侵袭并降低了Wnt/β-catenin信号分子β-catenin、细胞周期蛋白(Cyclin)D1、基质金属蛋白酶(MMP)-2和MMP-7的表达(均P<0.01)。体内实验显示,敲降METTL5减缓了移植瘤生长和Wnt/β-catenin信号活性。结论敲降METTL5能抑制TNBC细胞的增殖、迁移与侵袭,其作用可能与抑制Wnt/β-catenin信号通路有关。Aim To investigate the role and potential mechanism of methyltransferase-like 5(METTL5)in triple-negative breast cancer(TNBC).Methods The expression of METTL5 in TNBC tumor tissues and cell lines was detected by immunohistochemistry and Western blot.After shRNA targeting METTL5(shRNA-METTL5)was transfected into TNBC cells,cell proliferation,migration and invasion were detected by CCK-8,colony formation,wound healing and Transwell assays,respectively.Western blot was used to detect the expression of Wnt/β-catenin signaling-related key proteins.A xenograft tumor model was constructed to verify the effect of METTL5 knockdown on the growth of TNBC cells and Wnt/β-catenin signaling activity in vivo.Results The expression of METTL5 was up-regulated in TNBC tumor tissues and cell lines(P<0.01).Knockdown of METTL5 significantly inhibited the proliferation,migration and invasion of TNBC cells and reduced the expression of Wnt/β-catenin signaling moleculesβ-catenin,cyclin D1,matrix metalloproteinase(MMP)-2 and MMP-7(all P<0.01).Knockdown of METTL5 reduced tumor growth and Wnt/β-catenin signaling activity in vivo.Conclusions Knockdown of METTL5 can inhibit the proliferation,migration and invasion of TNBC cells,which may be related to the inhibition of Wnt/β-catenin signaling pathway.

关 键 词：三阴乳腺癌 甲基转移酶5 m6A甲基化 WNT/Β-CATENIN 增殖 迁移 侵袭 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学] R345.5[医药卫生—基础医学] R394.2R737.9