SERPINH1 modulates apoptosis by inhibiting P62 ubiquitination degradation to promote bone metastasis of prostate cancer

Autor: Chen Tang, Yiming Lai, Lingfeng Li, Min-yi Situ, Shurui Li, Bisheng Cheng, Yongming Chen, Zhen Lei, YanTing Ren, Jie Zhou, Yongxin Wu, Haitao Zhong, Kaiwen Li, Lexiang Zeng, Zhenghui Guo, Shengmeng Peng, Hai Huang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 8, Pp 110427- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.110427
Popis: Summary: 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.
Databáze: Directory of Open Access Journals