DNA methylation-mediated low expression of ZNF582 promotes the proliferation, migration, and invasion of clear cell renal cell carcinoma.

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.