2. Academic Validation
  3. USP10-mediated Ku70/80 stabilization inhibits PANoptosis and promotes chemoresistance in colorectal cancer

USP10-mediated Ku70/80 stabilization inhibits PANoptosis and promotes chemoresistance in colorectal cancer

  • Oncogene. 2025 Sep 18. doi: 10.1038/s41388-025-03570-2.
Penghang Lin # 1 2,  Chunlin Lin # 1 2,  Zuhong Teng 1 2 3 4,  Songyi Liu 1 2 3 4,  Xiang Lin 1 2 3 4,  Ruofan He 1 2 3 4,  Hengxin Yao 1 2 3 4,  Jianxin Ye 5 6,  Guangwei Zhu 7 8
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery 2 Section, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
  • 2 Department of Gastrointestinal Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
  • 3 Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
  • 4 Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
  • 5 Department of Gastrointestinal Surgery 2 Section, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. yejianxinfuyi@126.com.
  • 6 Department of Gastrointestinal Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. yejianxinfuyi@126.com.
  • 7 Department of Gastrointestinal Surgery 2 Section, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. zgwzsy@126.com.
  • 8 Department of Gastrointestinal Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. zgwzsy@126.com.
  • # Contributed equally.
PMID: 40968255 DOI: 10.1038/s41388-025-03570-2
Abstract

Chemotherapy is a widely used treatment for advanced colorectal cancer; however, its efficacy is often limited by chemotherapy resistance, the complex mechanisms of which remain poorly understood. Interestingly, we discovered that the expression levels of USP10 increase in tumor cells in response to chemotherapy, contributing to chemotherapy resistance. Under chemotherapy-induced stress, USP10 stabilizes the Ku70/80 complex in colorectal Cancer cells, promoting DNA repair, reducing intracellular ROS levels, and mitigating PANoptosis, which leads to chemotherapy resistance. Additionally, the promoter activity of USP10 is regulated by the non-coding RNA Linc01106. This study also confirmed that the absence of USP10 enhances chemotherapy sensitivity in colorectal Cancer cells, providing a potential strategy for overcoming chemotherapy resistance and improving therapeutic outcomes.

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