USP7介导的去泛素化作用可稳定JunD并激活AIFM2（FSP1），从而抑制黑色素瘤中的铁死亡。

Deubiquitination by USP7 Stabilizes JunD and Activates AIFM2 (FSP1) to Inhibit Ferroptosis in Melanoma.

作者信息

Xie Jiaheng, Ma Chenfeng, Zhao Songyun, Wu Dan, Zhang Pengpeng, Tang Qikai, Ni Tianyi, Yan Wei, Qi Min

机构信息

Department of Plastic Surgery, Shenzhen Hospital of Southern Medical University, Shenzhen, China; Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, China.

Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

出版信息

J Invest Dermatol. 2025 Apr 3. doi: 10.1016/j.jid.2025.03.018.

DOI:10.1016/j.jid.2025.03.018

PMID:40187679

Abstract

Ferroptosis resistance in melanoma cells is a key factor in melanoma progression, influenced by the tumor microenvironment. This study investigates the regulatory mechanisms of the USP7-JunD-AIFM2 pathway, which contributes to ferroptosis resistance in melanoma cells. We identified USP7 as a critical deubiquitinase that stabilizes the transcription factor JunD. Stabilized JunD, in turn, promotes the expression of AIFM2 (also known as FSP1), enhancing ferroptosis resistance in melanoma. Inhibition of USP7 led to JunD degradation and reduced AIFM2 levels, effectively sensitizing melanoma cells to ferroptosis both in vitro and in murine xenograft models. These findings underscore the role of the USP7-JunD-AIFM2 pathway in ferroptosis resistance and suggest that targeting USP7 could provide a potential therapeutic strategy against resistant melanoma.

摘要

黑色素瘤细胞中的铁死亡抗性是黑色素瘤进展的关键因素，受肿瘤微环境影响。本研究调查了USP7-JunD-AIFM2通路的调控机制，该通路有助于黑色素瘤细胞的铁死亡抗性。我们确定USP7是一种关键的去泛素化酶，可稳定转录因子JunD。稳定的JunD反过来促进AIFM2（也称为FSP1）的表达，增强黑色素瘤中的铁死亡抗性。抑制USP7导致JunD降解并降低AIFM2水平，在体外和小鼠异种移植模型中均有效地使黑色素瘤细胞对铁死亡敏感。这些发现强调了USP7-JunD-AIFM2通路在铁死亡抗性中的作用，并表明靶向USP7可能提供一种针对抗性黑色素瘤的潜在治疗策略。