GPX3 and nonpapillary renal cell carcinoma: To explore whether promoter methylation directly mediates GPX3 reduction in ccRCC, three methylated cell lines that showed downregulation of GPX3 were treated with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine with or without the histone deacetylase inhibitor trichostatin A. Results showed that 5-Aza treatment could restore GPX3 mRNA expression in ccRCC cells along with a decrease in methylated alleles, and the same results were observed in A + T treated-RCC cells (Figure 2A,B).