多梳抑制复合物1通过与核糖体蛋白L4结合并增加MDM2介导的p53泛素化来促进卵巢癌进展。

PRC1 promotes ovarian cancer progression by binding to RPL4 and increasing MDM2-mediated p53 ubiquitination.

作者信息

Xu Yinyin, Xu Jiaxing, Xu Kai, Zhang Cancan, Wang Fengmian, Zhang Rong, Zhu Pengfeng

机构信息

The Third Affiliated Hospital, Southern Medical University, Guangzhou, China; Department of Obstetrics and Gynecology, Shanghai Fengxian District Central Hospital, Shanghai, China.

Department of Gynecological Oncology, Zhongshan Hospital, Fudan University School of Medicine, Shanghai, China.

出版信息

Exp Cell Res. 2025 Apr 15;447(2):114509. doi: 10.1016/j.yexcr.2025.114509. Epub 2025 Mar 13.

DOI:10.1016/j.yexcr.2025.114509

PMID:40089132

Abstract

Ovarian cancer (OC) is one of the most fatal gynecological carcinomas, causing significant detriment to women's health. Protein regulator of cytokinesis 1 (PRC1) is a microtubule-associated protein that is found to be highly expressed in many different cancers. Despite this, the exact way in which PRC1 stimulates the growth of OC has yet to be completely understood. Our research demonstrated that PRC1 expression was increased in OC, which was closely related to poor prognosis. Moreover, PRC1 exhibited noteworthy efficacy in enhancing the proliferation and migration capacities of OC cells, as well as affecting the cell cycle in OC cells. Silencing PRC1 significantly suppressed OC growth in vivo. Mechanically, PRC1 could interact with RPL4, which caused a decrease in RPL4/MDM2 complex formation, resulting in the enhanced ubiquitination of p53 and a reduction of p53 proteins. These findings revealed that PRC1 was involved in the RPL4-MDM2-p53 pathway thus playing a tumorigenic role on OC.

摘要

卵巢癌（OC）是最致命的妇科癌症之一，对女性健康造成严重损害。胞质分裂蛋白调节剂1（PRC1）是一种微管相关蛋白，在许多不同癌症中均呈高表达。尽管如此，PRC1刺激OC生长的确切方式尚未完全明确。我们的研究表明，OC中PRC1表达增加，这与不良预后密切相关。此外，PRC1在增强OC细胞的增殖和迁移能力以及影响OC细胞的细胞周期方面表现出显著效果。沉默PRC1可显著抑制体内OC生长。从机制上讲，PRC1可与RPL4相互作用，导致RPL4/MDM2复合物形成减少，从而增强p53的泛素化并减少p53蛋白。这些发现揭示，PRC1参与RPL4-MDM2-p53通路，从而在OC中发挥致瘤作用。