2. Academic Validation
  3. Aging-associated ZNF573 methylation regulates RNF19B-PIK3CA ubiquitination to promote prostate cancer

Aging-associated ZNF573 methylation regulates RNF19B-PIK3CA ubiquitination to promote prostate cancer

  • Oncogene. 2025 Sep 19. doi: 10.1038/s41388-025-03579-7.
Yuqiu Ge # 1 2,  Peiyu Han # 2,  Yangyang Sun # 1 3,  Yuyu Chen 2,  Qianqian Shi 4,  Li Cui 5,  Qinbo Yuan 6 7,  Gaoxiang Ma 8 9
Affiliations

Affiliations

  • 1 Department of Urology, Pukou Hospital of Chinese Medicine Affiliated to China Pharmaceutical University, Nanjing, China.
  • 2 Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, China.
  • 3 Clinical Metabolomics Center, China Pharmaceutical University, Nanjing, China.
  • 4 Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
  • 5 Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, China. cuili_changzhou@163.com.
  • 6 Department of Urology, Pukou Hospital of Chinese Medicine Affiliated to China Pharmaceutical University, Nanjing, China. qinbo_yuan@126.com.
  • 7 Department of Urology, Wuxi Fifth People's Hospital, Wuxi, China. qinbo_yuan@126.com.
  • 8 Department of Urology, Pukou Hospital of Chinese Medicine Affiliated to China Pharmaceutical University, Nanjing, China. gaoxiang_ma@163.com.
  • 9 State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China. gaoxiang_ma@163.com.
  • # Contributed equally.
PMID: 40973794 DOI: 10.1038/s41388-025-03579-7
Abstract

Aging significantly influences the pathogenesis of prostate Cancer (PCa). Emerging evidence suggests that aging-related methylation changes play a critical role in PCa. However, the impact of aging-related DNA methylation in PCa remains largely unexplored. To identify hypermethylated sites associated with aging in PCa, we performed an epigenome-wide analysis using Illumina Human Methylation BeadChip arrays. The candidate methylation markers were further refined through least absolute shrinkage and selection operator (LASSO) regression and Random Forest model. Besides, we investigate the functional role of ZNF573 in PCa. Our analysis identified four aging-related CpG sites in the promoter region of ZNF573 that exhibited significant hypermethylation in PCa. These four DNA methylation markers effectively distinguished PCa from benign prostatic hyperplasia (BPH) with high AUC (0.847), which was superior to PSA. Furthermore, the expression of ZNF573 was notably down-regulated in PCa, and its overexpression significantly inhibited PCa cells proliferation and invasion both in vivo and in vitro. ZNF573 acting as a transcription factor promoted the expression of the E3 ubiquitin Ligase RNF19B, which regulated the ubiquitination of PIK3CA. These findings suggest that aging-related ZNF573 methylation could serve as a potential diagnostic biomarker for PCa, influencing the development and progression of PCa through the regulation of PIK3CA ubiquitination via RNF19B.

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