2. Academic Validation
  3. PPM1B degradation mediated by TRIM25 ubiquitination modulates cell cycle and promotes gastric cancer growth

PPM1B degradation mediated by TRIM25 ubiquitination modulates cell cycle and promotes gastric cancer growth

  • Sci Rep. 2025 Feb 20;15(1):6160. doi: 10.1038/s41598-025-89519-7.
Guang-Wei Zhu 1 2 3,  Hui Chen # 1 2 3,  Song-Yi Liu # 1 2 3,  Peng-Hang Lin 1 2 3 4,  Chun-Lin Lin 1 2 3 4,  Jian-Xin Ye 5 6 7
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery 2 Section, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
  • 2 Department of Gastrointestinal Surgery, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, China.
  • 3 Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
  • 4 Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China.
  • 5 Department of Gastrointestinal Surgery 2 Section, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China. yejianxinfuyi@126.com.
  • 6 Department of Gastrointestinal Surgery, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, China. yejianxinfuyi@126.com.
  • 7 Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China. yejianxinfuyi@126.com.
  • # Contributed equally.
PMID: 39979355 DOI: 10.1038/s41598-025-89519-7
Abstract

Protein Phosphatase PPM1B, a member of the serine/threonine Phosphatase family, has been implicated in various human cancers. In this study, our objective was to investigate the role of PPM1B in GC growth and explore the underlying mechanisms. Our findings revealed that PPM1B expression was downregulated in GC tissues, and higher levels of PPM1B expression were associated with improved overall survival in GC patients. Overexpression of PPM1B significantly inhibited cell proliferation, induced G1 phase cell cycle arrest, and suppressed tumor growth. Conversely, knockdown or knockout of PPM1B yielded opposite effects. Mechanistically, we identified that PPM1B exerted its inhibitory role in GC cell growth and cell cycle regulation through the TRIM25/PPM1B/CDK2 signaling pathway. Specifically, we demonstrated that TRIM25 physically interacts with PPM1B, leading to enhanced degradation of PPM1B and subsequent modulation of CDK2 phosphorylation and GC cell growth. PPM1B emerges as a potential prognostic biomarker and therapeutic target in GC. These findings hold clinical significance by offering opportunities to improve diagnosis and treatment strategies for GC patients. Furthermore, this study provides novel insights into the pathogenesis and progression of GC, expanding our understanding of this disease.

Keywords

Cell cycle; Gastric cancer; PPM1B; TRIM25; Tumor growth.

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