Lin Penghang, Lin Chunlin, Teng Zuhong, Liu Songyi, Lin Xiang, He Ruofan, Yao Hengxin, Ye Jianxin, Zhu Guangwei
Department of Gastrointestinal Surgery 2 Section, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Department of Gastrointestinal Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Oncogene. 2025 Sep 18. doi: 10.1038/s41388-025-03570-2.
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.
化疗是晚期结直肠癌广泛使用的治疗方法；然而，其疗效常受化疗耐药性限制，而化疗耐药的复杂机制仍知之甚少。有趣的是，我们发现USP10的表达水平在肿瘤细胞中因化疗而升高，这导致了化疗耐药性。在化疗诱导的应激下，USP10稳定结直肠癌细胞中的Ku70/80复合物，促进DNA修复，降低细胞内活性氧水平，并减轻PAN凋亡，从而导致化疗耐药。此外，USP10的启动子活性受非编码RNA Linc01106调控。本研究还证实，USP10缺失可增强结直肠癌细胞的化疗敏感性，为克服化疗耐药性和改善治疗效果提供了一种潜在策略。
