摘要
目的探讨G蛋白亚基Alpha O1(GNAO1)在脑胶质瘤组织中的表达及其调控脑胶质瘤细胞生物学行为的分子机制和对患者预后的影响。方法从癌症基因组图谱(TCGA)数据库和基因型-组织表达(GTEx)数据库下载706例脑胶质瘤患者和1152例正常脑组织的GNAO1转录组数据及相关临床资料,分析GNAO1在脑胶质瘤中的表达情况、与临床病理特征的相关性及其对患者生存预后的影响。以脑胶质瘤细胞(U-87MG和U251)作为对照组,稳定过表达GNAO1的U-87MG和U251细胞作为实验组,采用细胞计数法检测细胞增殖能力,使用划痕实验和Transwell实验评估细胞迁移和侵袭能力,并通过蛋白质印迹法检测上皮-间质转化相关标志物N-钙黏蛋白(N-cadherin)、E-钙黏蛋白(E-cadherin)、β-连环蛋白、α平滑肌肌动蛋白、基质金属蛋白酶2、基质金属蛋白酶9的蛋白相对表达水平。结果TCGA和GTEx数据库分析显示,GNAO1在脑胶质瘤中显著低表达且其低表达与患者不良预后有关。细胞实验结果表明,过表达GNAO1可显著抑制U-87MG和U251细胞增殖、迁移和侵袭能力。蛋白质印迹法结果显示,GNAO1过表达可下调间质型标志物N-cadherin和上调上皮型标志物E-cadherin蛋白的表达。结论GNAO1在脑胶质瘤中低表达,且其低表达与脑胶质瘤患者预后不良有关。在体外通过抑制上皮-间质转化过程可显著抑制脑胶质瘤细胞的增殖、迁移和侵袭能力。
Objective To analyze the expression level of G protein subunit alpha O1(GNAO1)in glioma tissues and its clinical significance,and to investigate the molecular mechanisms by which GNAO1 regulates the biological behaviors of glioma cells and the impact of GNAO1 on patient prognosis.Methods The GNAO1 transcriptomic data and clinical materials of 706 glioma patients and 1152 normal brain tissues were downloaded from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases,respectively.The expression patterns of GNAO1 in glioma,its correla-tion with clinicopathological features,and its impact on patient survival and prognosis were analyzed.In cellular experiments,glioma cell lines(U-87MG and U251)were used as the control group,and the U-87MG and U251 cells stably overexpressing GNAO1 were established as the experimental group.Cell proliferation was assessed using the cell counting method,while cell migration and invasion abilities were evaluated by scratch wound healing assay and Transwell assay,respectively.The relative protein expression levels of epithelial-mesenchymal transition(EMT)-related markers,including N-cadherin,E-cadherin,β-catenin,α-smooth muscle actin,matrix metalloproteinase(MMP)-2,and MMP-9,were detected by Western blot.Results Analysis of TCGA and GTEx databases revealed that GNAO1 was significantly down-regulated in glioma tissues,and its low expression was closely associated with poor prognosis of patients.Cellular experiments demonstrated that overexpression of GNAO1 significantly inhibited the proliferation,migration,and invasion abilities of U-87MG and U251.Western blot results showed that GNAO1 overexpression downregulated the expression of the mesenchymal marker N-cadherin and upregulated the expression of the epithelial marker E-cadherin.Conclusion GNAO1 is downre-gulated in glioma,and its low expression is associated with poor prognosis of glioma patients.In vitro,GNAO1 significantly inhibits the proliferation,migration,and invasion of glioma cells by suppressing the EMT process.
作者
刘雪
吴卉
吴琼
姚庆华
LIU Xue;WU Hui;WU Qiong;YAO Qinghua(Postgraduate Training Base Alliance,Wenzhou Medical University,Hangzhou 310022,China;不详)
出处
《浙江医学》
2025年第5期462-468,共7页
Zhejiang Medical Journal
基金
浙江省自然科学基金资助项目(LQ23H160008、LZ20H290001)。
