铁死亡诱导已成为前列腺癌（PCa）的一种有前途的治疗方法，无论是作为单一疗法还是与激素疗法相结合。因此，确定 PCa 细胞铁死亡的调节机制至关重要。我们之前的研究表明，PCa 细胞中上调的癌基因 HJURP 在肿瘤增殖中发挥作用。在这里，我们通过阐明 HJURP 在体外和体内通过 PRDX1/活性氧 (ROS) 途径抑制 PCa 细胞对铁死亡诱导剂的敏感性的新机制来扩展这些发现。从机制上讲，HJURP 通过 Cys327 和 Cys457 残基与 PRDX1 形成二硫键连接的中间体。这种二硫键结合促进 PRDX1 氧化还原循环并抑制其过度氧化。因此，HJURP 增强了 PRDX1 的过氧化物酶活性，导致 ROS 水平降低，随后抑制铁死亡诱导剂诱导的脂质过氧化。这些发现揭示了 HJURP/PRDX1 作为 PCa 患者铁死亡新治疗靶点和生物标志物的潜力。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Ferroptosis induction has emerged as a promising therapeutic approach for prostate cancer (PCa), either as a monotherapy or in combination with hormone therapy. Therefore, identifying the mechanisms regulating ferroptosis in PCa cells is essential. Our previous study demonstrated that HJURP, an oncogene upregulated in PCa cells, plays a role in tumor proliferation. Here, we expand these findings by elucidating a novel mechanism by which HJURP inhibits sensitivity to ferroptosis inducers in PCa cells via the PRDX1/reactive oxygen species (ROS) pathway in vitro and in vivo. Mechanistically, HJURP forms disulfide-linked intermediates with PRDX1 through Cys327 and Cys457 residues. This disulfide binding promotes PRDX1 redox cycling and inhibits its hyperoxidation. As a result, HJURP enhances the peroxidase activity of PRDX1, leading to a decrease in ROS levels and subsequently suppressing lipid peroxidation induced by ferroptosis inducers. These findings reveal the potential of HJURP/PRDX1 as novel therapeutic targets and biomarkers of ferroptosis in PCa patients.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.