G Protein γ subunit 7 loss contributes to progression of clear cell renal cell carcinoma

• Published in: Journal of cellular physiology 2019-11, Vol.234 (11), p.20002-20012
• Main Authors: Xu, Shan, Zhang, Haibao, Liu, Tianjie, Chen, Yule, He, Dalin, Li, Lei
• Format: Article
• Language: English
• Subjects: Bioinformatics; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; cell cycle; Cell Cycle - genetics; Cell Line, Tumor; Cell Proliferation - genetics; Clear cell-type renal cell carcinoma; Disease Progression; DNA methylation; Down-Regulation - genetics; E2F protein; G1 phase; Gene expression; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Gene set enrichment analysis; Genes; GEO; GNG7; GTP-Binding Protein gamma Subunits - genetics; GTP-Binding Protein gamma Subunits - metabolism; Homology; Humans; Kaplan-Meier Estimate; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Methylation; Mutation; Myc protein; Neoplasia; Original; Original s; Point mutation; Protein interaction; Protein Interaction Mapping; Proteins; RCC; Survival; Tumor suppressor genes
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.28597

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.