Li Ya, Zhou Fei, Xu Zhengmei
Department of Gynecology, Affiliated Hengyang Hospital of Hunan Normal University & Hengyang Central Hospital, Hengyang, No.12 Yancheng Road, Hengyang city, Hunan province, 421000, PR China.
Department of Gynecology, Affiliated Hengyang Hospital of Hunan Normal University & Hengyang Central Hospital, Hengyang, No.12 Yancheng Road, Hengyang city, Hunan province, 421000, PR China.
Transl Oncol. 2025 Jun;56:102386. doi: 10.1016/j.tranon.2025.102386. Epub 2025 Apr 18.
Ovarian cancer represents a significant threat to women's health. and ferroptosis is recognized as a potential natural inhibitor in cancer therapy, the regulatory mechanism of TRIM25 in ovarian cancer and its potential for regulating ferroptosis as a treatment remain unclear.
The role of TRIM25 in ovarian cancer was examined through functional gain- and loss-of-function assays both in vitro and in vivo, while its target genes were identified. The stability and ubiquitination sites of PIEZO1 were analyzed using protein docking and ubiquitination experiments.
TRIM25 is highly expressed in ovarian cancer and promotes the growth and metastasis of ovarian cancer cells both in vivo and in vitro. Mechanistically, it facilitates PIEZO1 degradation through ubiquitination-dependent proteasome activity, inhibits ferroptosis, and stimulates ovarian cancer cell growth.
Our study clearly shows that TRIM25 stimulates ovarian cancer by inducing K63-linked ubiquitination of PIEZO1, which suppresses ferroptosis and promotes excessive proliferation of ovarian cancer cells. Further research identified the ubiquitination modification site on PIEZO1, providing insights for ovarian cancer treatment.
卵巢癌对女性健康构成重大威胁。铁死亡被认为是癌症治疗中一种潜在的天然抑制剂，TRIM25在卵巢癌中的调控机制及其作为治疗手段调节铁死亡的潜力仍不清楚。
通过体外和体内的功能获得和功能丧失试验研究TRIM25在卵巢癌中的作用，同时鉴定其靶基因。利用蛋白质对接和泛素化实验分析PIEZO1的稳定性和泛素化位点。
TRIM25在卵巢癌中高表达，在体内和体外均促进卵巢癌细胞的生长和转移。机制上，它通过泛素化依赖性蛋白酶体活性促进PIEZO1降解，抑制铁死亡，并刺激卵巢癌细胞生长。
我们的研究清楚地表明，TRIM25通过诱导PIEZO1的K63连接泛素化来刺激卵巢癌，这抑制了铁死亡并促进了卵巢癌细胞的过度增殖。进一步的研究确定了PIEZO1上的泛素化修饰位点，为卵巢癌治疗提供了思路。
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