AIM2 通过 FOXO3a-ACSL4 轴调节的铁死亡促进肾细胞癌进展和舒尼替尼抗性。
AIM2 promotes renal cell carcinoma progression and sunitinib resistance through FOXO3a-ACSL4 axis-regulated ferroptosis.
发表日期：2023
作者：
Qi Wang, Su Gao, Yi Shou, Yujie Jia, Zhihao Wei, Yuenan Liu, Jian Shi, Daojia Miao, Qi Miao, Chuanyi Zhao, Chenchen Liu, Hongmei Yang, Tianbo Xu, Xiaoping Zhang
来源：
International Journal of Biological Sciences
摘要：
肾细胞癌（RCC）由于其快速进展成为人们健康的严重威胁，患者容易对靶向治疗产生抵抗力。缺失在黑色素瘤2（AIM2）是一种受体蛋白，最近被提出在各种疾病中起着重要作用。在本研究中，AIM2被确认为RCC的新生物标志物，通过炎症小体独立的方式促进了RCC的进展和舒尼替尼耐药性。在机械学上，AIM2促进FOXO3a磷酸化和蛋白酶体降解，从而减少其对ACSL4的转录效应，并抑制铁死亡。总之，AIM2通过FOXO3a-ACSL4轴调节的铁死亡促进了RCC的发展和舒尼替尼的耐药性，这可以为RCC的诊断和治疗提供新的思路和治疗靶点。©作者.
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.© The author(s).