DNA methylation and histone modifications are crucial for tissue homeostasis, and mutations in methylation-related genes like UTX and UTY are closely associated with cancer development. In renal cell carcinoma (RCC), defects in UTX and UTY have provided new therapeutic directions and insights into the understanding of the cancer's pathogenic mechanisms.
 In this study, we used dual siRNA (siUTX/siUTY) to knock down the UTX and UTY genes in three cell lines, resulting in enhanced cell proliferation, invasion, and migration abilities. Clinical data for RCC (n=312) were obtained from the TCGA database. The results indicated that, compared to the high UTX expression group, the low UTX expression group exhibited a significantly shortened progression-free survival (PFS). Similarly, the low UTX expression group also showed a significantly shortened overall survival (OS) compared to the high UTX expression group.
 In order to elucidate the role of UTX and UTY loss of function in the pathogenesis of RCC, we generated genetically engineered mice with kidney-specific deletions of Utx and Uty (UtxΔ, UtyΔ). These mice were then crossbred with mice carrying mutations closely associated with RCC, namely p53+/- and Vhl+/- mice. Ultimately, UtxΔ, UtyΔ, p53+/-, and Vhl+/- compound mice were created. To promote cancer development, mice were subcutaneously injected with iron (Fe) starting from 8-9 weeks of age. Kidney tissues were collected at regular intervals to observe the onset of cancer and changes in malignancy.
 Future research may focus on developing new treatment methods, diagnostic tools, and prevention strategies to improve the survival rate and quality of life for kidney cancer patients.