Zheng Fuchun, Li Sheng, Xiong Situ, Li Zhongqi, Yuan Ruize, Wang Zhipeng, Wan Hao, Liu Jiahao, Dong Qianxi, Liu Xiaoqiang, Pang Wan, Xi Haibo, Fu Bin, Xu Songhui
Jiangxi Provincial Key Laboratory of Urinary System Diseases, Department of Urology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
College of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai, China.
Cell Death Dis. 2025 Jun 10;16(1):443. doi: 10.1038/s41419-025-07758-y.
Bladder cancer (BCa) is a representative of urological cancer with a high recurrence and metastasis is the leading cause of death from BCa. The underlying mechanism of BCa metastasis remains poorly defined. Here, we found RNF41 was significantly downregulated in BCa tissue and low level of RNF41 is associated with BCa progression and poor prognosis. RNF41 knockdown promoted cell migration and invasion in both in vitro and in tail vein lung metastasis model, while ectopic RNF41 expression exhibited the opposite effects. Mechanically, we revealed that RNF41 directly interacted with NUDC and ubiquitinates NUDC to promote its degradation. Clinically, RNF41 was significantly downregulated in metastatic BCa tissues and negatively associated with NUDC expression. Furthermore, we identified that RNF41 promoted BCa lung metastasis through NUDC regulated β-tubulin depolymerization. In summary, these findings support that RNF41 was a tumor suppressor in BCa metastasis and highlights that targeting RNF41-NUDC-β-tubulin axis could be a valuable strategy to ameliorate BCa progression and metastasis.
膀胱癌（BCa）是泌尿系统癌症的代表，其高复发和转移是BCa死亡的主要原因。BCa转移的潜在机制仍不清楚。在此，我们发现RNF41在BCa组织中显著下调，且RNF41低水平与BCa进展及不良预后相关。在体外和尾静脉肺转移模型中，敲低RNF41均促进细胞迁移和侵袭，而异位表达RNF41则表现出相反的作用。机制上，我们揭示RNF41直接与NUDC相互作用并使其泛素化以促进其降解。临床上，RNF41在转移性BCa组织中显著下调且与NUDC表达呈负相关。此外，我们确定RNF41通过NUDC调节β-微管蛋白解聚促进BCa肺转移。总之，这些发现支持RNF41是BCa转移中的肿瘤抑制因子，并突出表明靶向RNF41-NUDC-β-微管蛋白轴可能是改善BCa进展和转移的有价值策略。
