低氧诱导因子HIF-1A调控GLUT3表达促进胶质瘤增殖的影响  

Effect of hypoxia inducible factor HIF⁃1A regulation GLUT3 expression promotes proliferation in glioma

作　　者：陈泰学 羊良旺 陈申波 高振忠 李争争 王艳 刘晓召 杨堃[1] CHEN Taixue;YANG Liangwang;CHEN Shenbo;GAO Zhenzhong;LI Zhengzheng;WANG Yan;LIU Xiaozhao;YANG Kun(Department of Neurosurgery,the First Affiliated Hospital of Hainan Medical University,Haikou 570102,China)

机构地区：[1]海南医学院第一附属医院神经外科,海南海口570102

出　　处：《海南医科大学学报》2025年第2期81-86,共6页Journal of Hainan Medical University

基　　金：海南省卫生健康行业科研项目(21A200080);国家自然科学基金资助项目(82060456);海南省“南海新星”科技创新人才平台项目(NHXXRCXM202351)。

摘　　要：目的:探讨乏氧环境下HIF-1A对胶质瘤GLUT3表达的影响及其机制。方法:CGGA数据库分析HIF-1A与GLUT3表达相关性及其对预后影响;CoCL2诱导胶质瘤细胞乏氧环境,Western blotting检测U251与U87细胞中GLUT3基因表达变化;Western blotting检测过表达HIF-1A对GLUT3及AKT蛋白表达的影响;体外CCK8细胞增殖实验检测shGLUT3对胶质瘤细胞增殖的影响。结果:CGGA数据库中HIF-1A与GLUT3的mRNA表达呈正相关(P=9.2e^(-05)),并且共表达对胶质瘤患者预后不良(P<0.0001)。Western blotting实验提示CoCL2诱导乏氧环境下HIF-1A与GLUT3基因表达升高,并随着CoCL2的浓度增加而表达增加;在过表达HIF-1A的细胞中GLUT3蛋白表达升高;在乏氧环境下U251和U87细胞中pAKT蛋白表达升高,而总AKT蛋白表达无变化,且AKT抑制剂能有效抑制HIF-1A上调的GLUT3表达。CCK8细胞增殖实验表明敲低GLUT3能显著抑制胶质瘤细胞的增殖(P<0.0001)。结论:胶质瘤中HIF-1A与GLUT3的表达呈正相关;乏氧环境下胶质瘤GLUT3表达升高;HIF-1A可能通过PI3K/AKT信号通路调节GLUT3基因的表达,促进胶质瘤的增殖。Objective:To investigate the effect of HIF-1A on GLUT3 expression of glioma in hypoxic environment.Methods:The correlation between HIF-1A and GLUT3 expression and its effect on prognosis were analyzed CGGA database.CoCL2 was used to induce hypoxic environment in glioma cells and Western blotting detect gene expression changes in U251 and U87 cells as well as the effects of overexpression HIF-1A on GLUT3 and AKT protein expression.CCK8 cell proliferation in vitro was used to detect shGLUT3 glioma effects of cell proliferation.Results:There was a positive correlation between HIF-1A and GLUT3 mRNA expression in the CGGA database(P=9.2e^(−05)),and coexpression had poor prognosis in glioma patients(P<0.0001).Western blotting experiments indicated that CoCL2 induced increased expression of HIF-1A and GLUT3 genes in hypoxic environment,increased expression with increasing concentration of CoCL2,increased expression GLUT3 protein in overexpressed cells and p-AKT protein surface in hypoxic environment up,while total AKT protein expression did not change,and AKT inhibitors could effectively inhibit HIF-1A upregulated GLUT3 expression.The proliferation of CCK8 cells showed that GLUT3 knockdown significantly inhibited the proliferation of glioma cells(P<0.0001).Conclusions:HIF-1A in glioma is positively correlated with the expression of GLUT3;the expression GLUT3 glioma is elevated in hypoxic environment;HIF-1A may regulate the expression of GLUT3 genes through the signaling pathway and promote glioma proliferation.

关 键 词：胶质瘤 氧诱导因子 葡萄糖转运酶3 细胞增殖 

分 类 号：R739.41[医药卫生—肿瘤]