HJURP inhibits sensitivity to ferroptosis inducers in prostate cancer cells by enhancing the peroxidase activity of PRDX1
Wenjie Lai,
Weian Zhu,
Jianjie Wu,
Jiongduan Huang,
Xiaojuan Li,
Yun Luo,
Yu Wang,
Hengda Zeng,
Mingqiang Li,
Xiaofu Qiu,
Xingqiao Wen
Affiliations
Wenjie Lai
Department of Urology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, 510317, PR China; Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR China; Laboratory of Biomaterials and Translational Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR China
Weian Zhu
Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR China
Jianjie Wu
Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR China
Jiongduan Huang
Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR China; Department of Urology, Shenshan Medical Center, Memorial Hospital of Sun Yat-sen University, Shanwei, Guangdong, 516600, PR China
Xiaojuan Li
Department of Health Care, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, 518101, PR China
Yun Luo
Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR China
Yu Wang
Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR China
Hengda Zeng
Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR China
Mingqiang Li
Laboratory of Biomaterials and Translational Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR China; Corresponding author. Laboratory of Biomaterials and Translational Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR China.
Xiaofu Qiu
Department of Urology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, 510317, PR China; Corresponding author.
Xingqiao Wen
Department of Urology, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou, 510080, PR China; Corresponding author. Department of Urology, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou, Guangdong, 510080, PR China.
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.
