OTUB2 promotes proliferation and metastasis of triple-negative breast cancer by deubiquitinating TRAF6.

OBJECTIVES: Deubiquitinase OTUB2 plays a critical role in the progression of various tumors. However, its specific role in triple-negative breast cancer (TNBC) remains unclear. This study aims to elucidate the biological function of OTUB2 in TNBC and uncover the underlying mechanisms. METHODS: First, we found that the expression of OTUB2 was upregulated in TNBC by bioinformatics analysis, we then validated its expression in TNBC tissues and cells using immunohistochemistry (IHC) and qPCR and plotted the survival curves by Kaplan-Meier method. Gene set enrichment analysis (GSEA) suggested that OTUB2 may be involved in tumor proliferation and metastasis. Further functional assays, including Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and wound healing assays, were performed to assess the effects of OTUB2 overexpression and knockdown on TNBC cell proliferation and migration. Additionally, UbiBrowser 2.0 was used to identify OTUB2 substrate proteins and western blotting was conducted to clarify the molecular mechanisms involved. RESULTS: Our results demonstrated that OTUB2 expression was elevated in TNBC and associated with poor prognosis. Overexpression of OTUB2 enhanced the proliferation and migration of TNBC cells, while its knockdown inhibited these processes. Moreover, OTUB2 stabilized tumor necrosis factor receptor-associated factor 6 (TRAF6) by deubiquitinating it, leading to activation of the protein kinase B (AKT) pathway. CONCLUSIONS: OTUB2 exerts its promoting effects on the progression of TNBC by activating the TRAF6/AKT pathway.