Guo Geng, Wang Shule, Hao Yining, Ren Yeqing, Wu Yongqiang, Zhang Jianping, Liu Dong
Department of Neurosurgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030000, P.R. China.
Oncol Lett. 2020 Jul;20(1):248-256. doi: 10.3892/ol.2020.11555. Epub 2020 Apr 21.
Aberrant expression of frequently rearranged in advanced T-cell lymphomas 1 (FRAT1) contributes to poor prognosis in a number of carcinomas. However, its role in glioma remains controversial. In the present study, gene expression profiling was performed using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) functional enrichment and ingenuity pathway analysis (IPA) to evaluate the differential expression of genes and proteins in FRAT1 knockdown U251 glioma cells in comparison with the control. Western blot analysis was conducted to assess the expression levels of FRAT1 and STAT1. A total of 895 downregulated genes were identified in FRAT1-silenced U251 cells. The most enriched processes determined by GO and KEGG analysis of the 895 differentially expressed genes were associated with proliferation, migration and invasion. According to IPA, significant canonical pathways, including the interferon, hepatic fibrosis and Wnt/β-catenin signaling pathways, were identified to be the major enriched pathways. The elevated expression of STAT1 in U251 cells was validated. These results highlighted the regulatory role of FRAT1 in glioma cells with upregulated STAT1 expression.
频繁重排在晚期T细胞淋巴瘤1(FRAT1)中的异常表达导致多种癌症的预后不良。然而,其在胶质瘤中的作用仍存在争议。在本研究中,利用京都基因与基因组百科全书(KEGG)、基因本体论(GO)功能富集和 Ingenuity 通路分析(IPA)进行基因表达谱分析,以评估与对照相比,FRAT1敲低的U251胶质瘤细胞中基因和蛋白质的差异表达。进行蛋白质印迹分析以评估FRAT1和STAT1的表达水平。在FRAT1沉默的U251细胞中总共鉴定出895个下调基因。通过对这895个差异表达基因进行GO和KEGG分析确定的最富集过程与增殖、迁移和侵袭相关。根据IPA,包括干扰素、肝纤维化和Wnt/β-连环蛋白信号通路在内的重要经典通路被确定为主要富集通路。U251细胞中STAT1的表达升高得到验证。这些结果突出了FRAT1在STAT1表达上调的胶质瘤细胞中的调节作用。