USP43 promotes lymphatic metastasis of bladder cancer by regulation of ZBTB7A.

Lymphatic metastasis is the most common route of dissemination in bladder cancer and is closely associated with poor clinical outcomes, posing a major challenge to effective treatment. Therefore, identifying the key initiators and regulators of lymphatic metastasis in bladder cancer may provide promising targets for its prevention and therapy. In this study, we report that USP43 is highly expressed in lymph node metastatic bladder cancer. USP43 promotes lymphangiogenesis and lymph node metastasis in both in vitro and in vivo models. Mechanistically, USP43 deubiquitinates and thereby stabilized ZBTB7A. As a transcription factor, ZBTB7A promotes lymphangiogenesis and facilitates lymph node metastasis by upregulating the transcription of VEGFA and activating AKT pathway. Collectively, our findings reveal that the USP43/ZBTB7A axis plays a crucial role in promoting lymphatic metastasis of bladder cancer, offering potential therapeutic and preventive strategies for lymph node metastatic bladder cancer.