Research Paper Volume 16, Issue 8 pp 6757—6772
USP15 facilitates the progression of bladder cancer by amplifying the activation of the NF-κB signaling pathway
- 1 Department of Ophthalmology, Second Affiliated Hospital of Nanchang University, Nanchang, China
- 2 Department of Emergency Medicine, Emergency and Critical Care Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
- 3 Department of Urology, Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Jinhua, China
- 4 Department of Ophthalmology, The First Affiliated Hospital, Sun-Yat-sen University, Guangzhou, China
- 5 Department of Urology, Second Affiliated Hospital of Nanchang University, Nanchang, China
Received: August 15, 2023 Accepted: November 21, 2023 Published: March 28, 2024
https://doi.org/10.18632/aging.205696How to Cite
Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
USP15, a pivotal member of the deubiquitinase family, plays a crucial role in orchestrating numerous vital biological processes, including the regulation of NF-κB signaling pathway and deubiquitination of proto-oncogenes. In various cancers, USP15 has been validated to exhibit up-regulated expression, impacting the initiation and progression of cancer. However, its precise mechanism in bladder cancer remains elusive. Our study shed light on the significant overexpression of USP15 in bladder cancer cells compared to normal bladder cells, correlating with a poorer prognosis for bladder cancer patients. Strikingly, attenuation of USP15 expression greatly attenuated the proliferation, migration, and invasion of bladder cancer cells. Moreover, upregulation of USP15 was found to drive cancer progression through the activation of the NF-κB signaling pathway. Notably, USP15 directly deubiquitinates BRCC3, heightening its expression level, and subsequent overexpression of BRCC3 counteracted the antitumoral efficacy of USP15 downregulation. Overall, our findings elucidated the carcinogenic effects of USP15 in bladder cancer, primarily mediated by the excessive activation of the NF-κB signaling pathway, thereby promoting tumor development. These results underscore the potential of USP15 as a promising therapeutic target for bladder cancer in the future.