Mengyu Ding1, Qiong Wang1, Wenwen Zhu1, Jian Chang1, Hui Liao1, Geqiong Xiao2. 1. Oncology department, Affiliated Hospital of Shaoxing University, 999 Zhongxing South Road, Yuecheng District, Shaoxing, 312099, People's Republic of China. 2. Oncology department, Affiliated Hospital of Shaoxing University, 999 Zhongxing South Road, Yuecheng District, Shaoxing, 312099, People's Republic of China. teatilsvm@outlook.com.
Abstract
OBJECTIVE: The methylation of DNA promoter region mediates the low expression of many tumor suppressor genes and plays an essential part in cancer progression. We investigated methylation and expression of ZNF582 in clear cell renal cell carcinoma (ccRCC), and to study the function of ZNF582 in ccRCC cells. METHODS: Methylation data and mRNA expression data of TCGA-KIRC were obtained from TCGA database to screen methylation-driven genes. Survival analysis and gene set enrichment analysis (GSEA) were done for the target gene. The methylation degree and mRNA level of ZNF582 in ccRCC cell line were detected by methylation-specific PCR (MSP) and qRT-PCR, respectively. Effects of overexpression of ZNF582 on ccRCC cells were assessed via CCK-8, flow cytometry, wound healing, Transwell, and cell adhesion assays. RESULTS: Eighteen methylation-driven genes were identified via bioinformatics methods. Among them, ZNF582 was noticeably hypermethylated and lowly expressed in tumor tissue, and ZNF582 methylation and expression levels were pronouncedly associated with prognosis and clinical stage. MSP also displayed that the ZNF582 DNA promoter region was hypermethylated in ccRCC cells, and the mRNA expression of ZNF582 was dramatically elevated after demethylation. In vitro cell experiments disclosed that overexpression of ZNF582 markedly hindered cell proliferation, invasion, migration, and fostered cell apoptosis and adhesion of ccRCC. CONCLUSION: ZNF582 was hypermethylated in ccRCC, which mediated its low level. Overexpression of ZNF582 inhibited tumor cell proliferation, migration and invasion. This study generates novel ideas for ccRCC diagnosis and treatment.
OBJECTIVE: The methylation of DNA promoter region mediates the low expression of many tumor suppressor genes and plays an essential part in cancer progression. We investigated methylation and expression of ZNF582 in clear cell renal cell carcinoma (ccRCC), and to study the function of ZNF582 in ccRCC cells. METHODS: Methylation data and mRNA expression data of TCGA-KIRC were obtained from TCGA database to screen methylation-driven genes. Survival analysis and gene set enrichment analysis (GSEA) were done for the target gene. The methylation degree and mRNA level of ZNF582 in ccRCC cell line were detected by methylation-specific PCR (MSP) and qRT-PCR, respectively. Effects of overexpression of ZNF582 on ccRCC cells were assessed via CCK-8, flow cytometry, wound healing, Transwell, and cell adhesion assays. RESULTS: Eighteen methylation-driven genes were identified via bioinformatics methods. Among them, ZNF582 was noticeably hypermethylated and lowly expressed in tumor tissue, and ZNF582 methylation and expression levels were pronouncedly associated with prognosis and clinical stage. MSP also displayed that the ZNF582 DNA promoter region was hypermethylated in ccRCC cells, and the mRNA expression of ZNF582 was dramatically elevated after demethylation. In vitro cell experiments disclosed that overexpression of ZNF582 markedly hindered cell proliferation, invasion, migration, and fostered cell apoptosis and adhesion of ccRCC. CONCLUSION: ZNF582 was hypermethylated in ccRCC, which mediated its low level. Overexpression of ZNF582 inhibited tumor cell proliferation, migration and invasion. This study generates novel ideas for ccRCC diagnosis and treatment.
Authors: M R Morris; C J Ricketts; D Gentle; F McRonald; N Carli; H Khalili; M Brown; T Kishida; M Yao; R E Banks; N Clarke; F Latif; E R Maher Journal: Oncogene Date: 2010-12-06 Impact factor: 9.867
Authors: Iris J H van Vlodrop; Sophie C Joosten; Tim De Meyer; Kim M Smits; Leander Van Neste; Veerle Melotte; Marcella M L L Baldewijns; Leo J Schouten; Piet A van den Brandt; Jana Jeschke; Joo Mi Yi; Kornel E Schuebel; Nita Ahuja; James G Herman; Maureen J Aarts; Fred T Bosman; Wim Van Criekinge; Manon van Engeland Journal: Clin Cancer Res Date: 2016-10-18 Impact factor: 12.531