Xu Anqi, Wang Xizhao, Zeng Yu, Zhou Mingfeng, Yi Renhui, Wu Zhiyong, Lin Jie, Song Ye
Department of Neurosurgery, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, PR China.
Department of Neurosurgery, The First Hospital of Quanzhou Affiliated to Fujian Medical University Quanzhou 362000, Fujian, PR China.
Int J Clin Exp Pathol. 2018 Oct 1;11(10):4827-4835. eCollection 2018.
This study aimed to reveal the correlation of increased TEA domain transcription factor 4 (TEAD4) expression and disease prognosis in glioma. The expression data of TEAD4 mRNA in glioma were collected from GEO database (GSE4290), and the expression of TEAD4 protein in glioma was confirmed using western blot and Immunohistochemistry. Kaplan-Meier analysis with the log-rank test was used to reveal the correlation of TEAD4 expression level and patients' survival. The effects of TEAD4 on migration and invasion were separately examined by Transwell assay and Boyden assay. Gene set enrichment analysis (GSEA) was performed to predict the possible biological function of TEAD4 in glioma. The results showed that TEAD4 mRNA and protein expression were upregulated in glioma tissues compared to normal brain tissues. Furthermore, overexpression of TEAD4 correlated with poor prognosis in glioma patients. Knockdown of TEAD4 markedly inhibited glioma cells migration and invasion in vitro. Consistent with the result that TEAD4 was associated with epithelial-mesenchymal transition (EMT) closely by GESA, knockdown of TEAD4 resulted in N-cadherin, vimentin and Slug downregulated but E-cadherin upregulated. Our study indicated that overexpression of TEAD4 may represent as a potential unfavorable marker for poor survival and prognosis in glioma. Knockdown of TEAD4 led to suppressed glioma migration and invasion.
本研究旨在揭示胶质瘤中TEA结构域转录因子4(TEAD4)表达增加与疾病预后的相关性。从GEO数据库(GSE4290)收集胶质瘤中TEAD4 mRNA的表达数据,并使用蛋白质免疫印迹法和免疫组织化学法确认胶质瘤中TEAD4蛋白的表达。采用Kaplan-Meier分析和对数秩检验来揭示TEAD4表达水平与患者生存的相关性。通过Transwell实验和博伊登实验分别检测TEAD4对迁移和侵袭的影响。进行基因集富集分析(GSEA)以预测TEAD4在胶质瘤中的可能生物学功能。结果显示,与正常脑组织相比,胶质瘤组织中TEAD4 mRNA和蛋白表达上调。此外,TEAD4的过表达与胶质瘤患者的不良预后相关。敲低TEAD4可显著抑制胶质瘤细胞在体外的迁移和侵袭。与GESA结果一致,即TEAD4与上皮-间质转化(EMT)密切相关,敲低TEAD4导致N-钙黏蛋白、波形蛋白和Slug下调,但E-钙黏蛋白上调。我们的研究表明,TEAD4的过表达可能是胶质瘤患者生存和预后不良的潜在不利标志物。敲低TEAD4导致胶质瘤迁移和侵袭受到抑制。