AIM2 promotes renal cell carcinoma progression and sunitinib resistance through FOXO3a-ACSL4 axis-regulated ferroptosis

Renal cell carcinoma (RCC) is a serious threat to people's health due to its rapid progression, and patients easily develop resistance to targeted therapy.The absent in melanoma 2 (AIM2) is a receptor protein that has recently been proposed to play an important role in various diseases.In this study, AIM2 was identified as a new biomarker of RCC and promoted RCC progression and sunitinib resistance in an inflammasome-independent manner.Mechanistically, AIM2 promoted FOXO3a phosphorylation and proteasome degradation, thereby reducing its transcriptional effect on ACSL4 and inhibiting ferroptosis.In summary, AIM2 promoted RCC progression and sunitinib resistance through FOXO3a-ACSL4 axis-regulated ferroptosis, which could provide new ideas and therapeutic targets for RCC diagnosis and treatment.