Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China.
Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, P.R. China.
J Cell Physiol. 2019 Nov;234(11):20002-20012. doi: 10.1002/jcp.28597. Epub 2019 Apr 3.
Clear cell renal cell carcinoma (ccRCC) is a common urinary neoplasm, looking for useful candidates to establish scientific foundation for the therapy of ccRCC is urgent. We downloaded genomic profiles of GSE781, GSE6244, GSE53757, and GSE66271 from the Gene Expression Omnibus (GEO) database. GEO2R was used to analyze the derivative genes, while hub genes were screened by protein-protein interactions and cytoscape. Further, overall survival, gene methylation, gene mutation, and gene expression were all analyzed using bioinformatics tools. Colony formation and cell-cycle assay were used to detect the biological function of GNG7 in vitro. We found that GNG7 was downregulated in ccRCC tissues and negatively associated with overall survival in ccRCC patients. We also found that promoter methylation and frequent gene mutation were responsible for GNG7 gene suppression. GNG7 low expression was related to upregulation of enhancer of zeste homolog 2 and downregulation of disabled homolog 2-interacting protein. Further, Gene Set Enrichment Analysis results showed that mTOR1, E2F, G2M, and MYC pathways were all significantly altered in response to GNG7 low expression. In vitro, A498 and 786-O cells in which GNG7 expression was silenced, exhibited a lower G1 phase when compared to the negative control cells. Taken together, our findings suggest that GNG7 is a tumor suppressor gene in ccRCC progression and represents a novel candidate for ccRCC treatment.
透明细胞肾细胞癌 (ccRCC) 是一种常见的泌尿系统肿瘤,寻找有用的候选物来为 ccRCC 的治疗建立科学基础迫在眉睫。我们从基因表达综合数据库 (GEO) 下载了 GSE781、GSE6244、GSE53757 和 GSE66271 的基因组图谱。使用 GEO2R 分析衍生基因,使用蛋白质-蛋白质相互作用和 cytoscape 筛选枢纽基因。进一步,使用生物信息学工具分析总生存、基因甲基化、基因突变和基因表达。集落形成和细胞周期分析用于体外检测 GNG7 的生物学功能。我们发现 GNG7 在 ccRCC 组织中下调,与 ccRCC 患者的总生存率呈负相关。我们还发现启动子甲基化和频繁的基因突变是导致 GNG7 基因抑制的原因。GNG7 低表达与增强子结合蛋白同源物 2 的上调和Disabled homolog 2-interacting protein 的下调有关。进一步,基因集富集分析结果表明,mTOR1、E2F、G2M 和 MYC 通路都因 GNG7 低表达而发生显著改变。在体外,沉默 GNG7 表达的 A498 和 786-O 细胞与阴性对照细胞相比,G1 期较低。总之,我们的研究结果表明,GNG7 是 ccRCC 进展中的一种肿瘤抑制基因,是 ccRCC 治疗的新候选物。