Tang Chen, Lai Yiming, Li Lingfeng, Situ Min-Yi, Li Shurui, Cheng Bisheng, Chen Yongming, Lei Zhen, Ren YanTing, Zhou Jie, Wu Yongxin, Zhong Haitao, Li Kaiwen, Zeng Lexiang, Guo Zhenghui, Peng Shengmeng, Huang Hai
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China.
Department of Urology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong 518052, P.R. China.
iScience. 2024 Jul 10;27(8):110427. doi: 10.1016/j.isci.2024.110427. eCollection 2024 Aug 16.
Prostate cancer (PCa) is one of the most prevalent urogenital malignancies. Bone metastasis from PCa reduces patient survival rates significantly. There currently exists no effective treatment for bone metastatic PCa, and the underlying mechanisms remain unclear. This study performed transcriptomic screening on PCa bone metastasis specimens and intersection analysis in public databases and identified SERPINH1 as a potential target for treatment. SERPINH1 was found to be upregulated in PCa bone metastases and with poor prognosis, high Gleason score, and advanced metastatic status. SERPINH1 induced PCa cells' bone metastasis , promoted their proliferation, and mitigated apoptosis. Mechanistically, SERPINH1 bound to P62, reducing TRIM21-mediated K63-linked ubiquitination degradation of P62 and promoting proliferation and resistance to apoptosis of PCa. This study suggests the regulation of ubiquitination degradation of P62 by SERPINH1 that promotes PCa bone metastasis and can be considered as a potential target for treatment of bone metastatic PCa.
前列腺癌（PCa）是最常见的泌尿生殖系统恶性肿瘤之一。PCa发生骨转移会显著降低患者生存率。目前对于骨转移性PCa尚无有效的治疗方法，其潜在机制仍不清楚。本研究对PCa骨转移标本进行了转录组筛选，并在公共数据库中进行了交叉分析，确定SERPINH1为潜在的治疗靶点。研究发现SERPINH1在PCa骨转移中上调，且与预后不良、高Gleason评分和晚期转移状态相关。SERPINH1诱导PCa细胞发生骨转移，促进其增殖，并减轻细胞凋亡。机制上，SERPINH1与P62结合，减少TRIM21介导的P62的K63连接的泛素化降解，促进PCa的增殖和抗凋亡能力。本研究提示SERPINH1对P62泛素化降解的调控促进了PCa骨转移，可被视为治疗骨转移性PCa的潜在靶点。
