SUV39H1 deficiency suppresses clear cell renal cell carcinoma growth by inducing ferroptosis.

Clear cell renal cell carcinoma (ccRCC) is a common kidney malignancy characterized by a poor prognosis. Suppressor of variegation 3-9 homolog 1 (), which encodes a histone H3 lysine 9 methyltransferase, has been reported to act as an oncogene in many cancers. However, it is unclear whether is involved in ccRCC. Here, we report that expression is frequently upregulated in ccRCC tumors and is significantly correlated with ccRCC progression. expression level is an independent risk factor for cancer prognosis, and integration with several known prognostic factors predicted ccRCC patient prognosis with improved accuracy than the conventional SSIGN (stage, size, grade and necrosis) prognostic model. Mechanistically, we discovered that siRNA knockdown or pharmacological inhibition of induced iron accumulation and lipid peroxidation, leading to ferroptosis that disrupted ccRCC cell growth and . We also show that deficiency modulated the H3K9me3 status of the (dipeptidyl-peptidase-4) gene promoter, resulting in upregulation of its expression that contributes to ferroptosis. Taken together, our findings provide the mechanistic insight into -dependent epigenetic control of ccRCC tumor growth and indicate that may serve as a potential therapeutic target for ccRCC treatment.