窖蛋白-1通过增强氧连接的N-乙酰葡糖胺糖基转移酶表达诱导小鼠肝癌细胞的迁移和侵袭  

Upregulation of OGT by Caveolin-1 Promotes Mouse Hepatocellular Carcinoma Cells Migration and Invasion

作　　者：王玲燕 王语涵 张程[1] 陈茜茜[1] 黄煌 李文利[1] 张嘉宁[1] 刘宇博[1] WANG Ling-Yan;WANG Yu-Han;ZHANG Cheng;CHEN Xi-Xi;HUANG Huang;LI Wen-Li;ZHANG Jia-Ning;LIU Yu-Bo(Research Group of Biology,School of Life and Pharmaceutical Sciences,Dalian University of Technology,Panjin 124221,Liaoning,China)

机构地区：[1]大连理工大学生命科学与药学学院生物学教研室,辽宁盘锦124221

出　　处：《中国生物化学与分子生物学报》2021年第8期1062-1068,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No.31570802,31870793);中央高校基本科研业务费(No.DUT20YG130,DUT20YG116)资助。

摘　　要：窖蛋白-1(caveolin-1,Cav-1)是胞膜窖的主要结构和功能蛋白质,参与调控多种细胞信号转导过程。然而,Cav-1调节蛋白质糖基化修饰和肿瘤转移作用机制尚不明确。本研究在小鼠肝癌细胞中证明,Cav-1能够促进蛋白质的氧连接的N-乙酰葡糖胺(O-linked N-acetylglucosamine,O-GlcNAc)糖基化及其O-GlcNAc转移酶(O-GlcNAc transferase,OGT)的表达,增强了小鼠肝癌细胞的迁移和侵袭潜能。RT-qPCR、Western印迹和双荧光素酶报告基因结果显示,Cav-1通过下调转录因子RUNX2表达,抑制了miR24的转录(P<0.05)。随后研究结果表明,miR24能够靶向Ogt mRNA 3′-UTR并抑制其表达(P<0.05)。这使得Cav-1通过RUNX2/miR24正向调控OGT的表达和O-GlcNAc糖基化,最终导致小鼠肝癌细胞迁移和侵袭潜能增加。这些结果揭示了Cav-1调控糖基转移酶OGT表达和蛋白质O-GlcNAc糖基化的新机制,为肝癌的发生发展机制研究提供了新的理论和实验依据。Caveolin-1(Cav-1),a major structural protein of caveolae,is implicated in the vesicular uptake processes of transcytosis and cell signaling.However,its role in modulating protein glycosylation and tumor metastasis remains to be further elucidated.In the present study,it was shown that Cav-1 promotes the expression of O-GlcNAcylation and O-GlcNAc transferase(OGT),and triggers the invasion and metastasis of hepatocellular carcinoma(HCC)cells.The results of RT-qPCR,Western blot and dual luciferase reporter assay showed that Cav-1 negatively regulated the expression of transcription factor RUNX2 in HCC.Subsequently,this results in attenuate RUNX2-induced transcription of miR24.miR24 suppresses mouse HCC cells invasion and metastasis via directly targeting Ogt mRNA 3′UTR.This research provides evidence of Cav-1-mediated OGT expression and O-GlcNAc(O-linked N-acetylglucosamine)elevation.These data give insight into a novel mechanism of HCC occurrence and development.

关 键 词：肝癌 窖蛋白-1 糖基转移酶 氧连接的N-乙酰葡糖胺 

分 类 号：Q7[生物学—分子生物学] Q5