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

Acta Pharmaceutica Sinica B

Jin Zhang¹  Wei He²  Jianfeng Wang³  Yiran Huang³  Wei Xue³  Xiaomao Yin³ 

[1] Corresponding authors.;Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China;Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China;

关键词: Clear cell renal cell carcinoma;    SUV39H1;    Progression;    Prognostic model;    Ferroptosis;    DPP4;   

DOI  :  

来源: DOAJ

【 摘 要 】

Clear cell renal cell carcinoma (ccRCC) is a common kidney malignancy characterized by a poor prognosis. Suppressor of variegation 3–9 homolog 1 (SUV39H1), which encodes a histone H3 lysine 9 methyltransferase, has been reported to act as an oncogene in many cancers. However, it is unclear whether SUV39H1 is involved in ccRCC. Here, we report that SUV39H1 expression is frequently upregulated in ccRCC tumors and is significantly correlated with ccRCC progression. SUV39H1 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 SUV39H1 induced iron accumulation and lipid peroxidation, leading to ferroptosis that disrupted ccRCC cell growth in vitro and in vivo. We also show that SUV39H1 deficiency modulated the H3K9me3 status of the DPP4 (dipeptidyl-peptidase-4) gene promoter, resulting in upregulation of its expression that contributes to ferroptosis. Taken together, our findings provide the mechanistic insight into SUV39H1-dependent epigenetic control of ccRCC tumor growth and indicate that SUV39H1 may serve as a potential therapeutic target for ccRCC treatment.

【 授权许可】

Unknown