iScience (Aug 2024)
SERPINH1 modulates apoptosis by inhibiting P62 ubiquitination degradation to promote bone metastasis of prostate cancer
- 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
Affiliations
- Chen Tang
- 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
- Yiming Lai
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Clinical Research Center for Urological Diseases, Guangzhou 510120, Guangdong, P.R. China; Department of Urology, the Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, Xinjiang, P.R. China
- Lingfeng Li
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China
- Min-yi Situ
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China
- Shurui Li
- Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China
- Bisheng Cheng
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China
- Yongming Chen
- Beijing Hospital, National Center of Gerontology Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, Dongcheng, P.R. China
- Zhen Lei
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China
- YanTing Ren
- Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China
- Jie Zhou
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China
- Yongxin Wu
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China
- Haitao Zhong
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China
- Kaiwen Li
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Clinical Research Center for Urological Diseases, Guangzhou 510120, Guangdong, P.R. China
- Lexiang Zeng
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Clinical Research Center for Urological Diseases, Guangzhou 510120, Guangdong, P.R. China
- Zhenghui Guo
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Clinical Research Center for Urological Diseases, Guangzhou 510120, Guangdong, P.R. China; Corresponding author
- Shengmeng Peng
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Clinical Research Center for Urological Diseases, Guangzhou 510120, Guangdong, P.R. China; Corresponding author
- Hai Huang
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, P.R. China; Guangdong Provincial Clinical Research Center for Urological Diseases, Guangzhou 510120, Guangdong, P.R. China; Department of Urology, the Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, Xinjiang, P.R. China; Corresponding author
- Journal volume & issue
-
Vol. 27,
no. 8
p. 110427
Abstract
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.