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<p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年9月18日

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  • Penghang Lin,
  • Chunlin Lin,
  • Zuhong Teng,
  • Songyi Liu,
  • Xiang Lin,
  • Ruofan He,
  • Hengxin Yao,
  • Jianxin Ye,
  • Guangwei Zhu

摘要

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.