泛素特异性肽酶32（USP32）在肿瘤中的调控意义重大，然而，USP32在非小细胞肺癌（NSCLC）中的生物学作用和调控机制仍不清楚。根据我们的研究，USP32 在 NSCLC 细胞系和组织中强烈表达，并与 NSCLC 患者的不良预后相关。干扰 USP32 可显着抑制 NSCLC 细胞增殖、迁移潜力和 EMT 发展；另一方面，USP32过度表达则产生相反的效果。为了进一步阐明USP32在NSCLC中的作用机制，我们筛选了H1299细胞的相互作用蛋白，发现USP32与BAG3（Bcl2相关的athanogene 3）相互作用，并以去泛素化活性依赖性方式去泛素化和稳定BAG3。从功能上讲，BAG3表达的恢复消除了USP32沉默的抗肿瘤作用。此外，USP32 通过稳定 BAG3 来增加 NSCLC 细胞中 RAF/MEK/ERK 信号通路的磷酸化水平。总之，这些发现表明 USP32 对 NSCLC 的发展至关重要，并且可以为未来 NSCLC 患者的临床诊断和管理提供理论框架。© 2024。作者。

The regulatory significance of ubiquitin-specific peptidase 32 (USP32) in tumor is significant, nevertheless, the biological roles and regulatory mechanisms of USP32 in non-small cell lung cancer (NSCLC) remain unclear. According to our research, USP32 was strongly expressed in NSCLC cell lines and tissues and was linked to a bad prognosis for NSCLC patients. Interference with USP32 resulted in a significant inhibition of NSCLC cell proliferation, migration potential, and EMT development; on the other hand, USP32 overexpression had the opposite effect. To further elucidate the mechanism of action of USP32 in NSCLC, we screened H1299 cells for interacting proteins and found that USP32 interacts with BAG3 (Bcl2-associated athanogene 3) and deubiquitinates and stabilizes BAG3 in a deubiquitinating activity-dependent manner. Functionally, restoration of BAG3 expression abrogated the antitumor effects of USP32 silencing. Furthermore, USP32 increased the phosphorylation level of the RAF/MEK/ERK signaling pathway in NSCLC cells by stabilizing BAG3. In summary, these findings imply that USP32 is critical to the development of NSCLC and could offer a theoretical framework for the clinical diagnosis and management of NSCLC patients in the future.© 2024. The Author(s).