前列腺癌（PCa）是最常见的泌尿生殖系统恶性肿瘤之一。 PCa 骨转移显着降低患者生存率。目前骨转移性前列腺癌尚无有效治疗方法，其潜在机制尚不清楚。这项研究对 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，并将 SERPINH1 确定为潜在的治疗靶点。研究发现，SERPINH1 在 PCa 骨转移中表达上调，预后不良、格里森评分高、转移状态晚期。 SERPINH1 在体内诱导 PCa 细胞骨转移，促进其增殖，并减轻细胞凋亡。从机制上讲，SERPINH1 与 P62 结合，减少 TRIM21 介导的 K63 相关的 P62 泛素化降解，促进 PCa 的增殖和抗凋亡。这项研究表明，SERPINH1 调节 P62 的泛素化降解，促进 PCa 骨转移，可被视为治疗骨转移性 PCa 的潜在靶点。© 2024 作者。

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 in vivo, 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.© 2024 The Authors.