Abstract

Ubiquitin D, a ubiquitin-like protein, functions as a potential tumor promoter in various cancers. However, its biological role and clinical significance in breast cancer remain unclear. In this study, we evaluated UBD expression in malignant and normal breast tissues using bioinformatics databases. Analysis of clinical specimens showed that UBD expression was significantly higher in primary breast cancer tissues than in normal breast tissues and was closely associated with key clinicopathological features in affected patients. Subsequently, breast cancer cell line models were established to assess the impact of UBD on malignant properties in vitro. KEGG pathway analysis indicated that differentially expressed genes were significantly enriched in the PI3K/AKT signaling pathway. Western blot analysis was performed to examine changes in EMT-related markers and key signaling molecules involved in the PI3K/AKT pathway in breast cancer cells. The PI3K/AKT agonist 740Y-P and inhibitor LY294002 were employed to determine the contribution of this pathway to EMT regulation in breast cancer cells. The results demonstrated that EMT signature-derived ssGSEA scores indicated UBD had the strongest positive correlation with the EMT process, and that UBD enhanced the expression of EMT-related markers in breast cancer cells. The pathway inhibitor LY294002 suppressed UBD-induced increases in migration and invasion, as well as the expression of EMT-related markers. In contrast, the agonist 740Y-P restored the decreased migration, invasion, and EMT phenotypes induced by UBD knockdown. Collectively, our data demonstrated that UBD plays a critical role in the malignant progression of breast cancer, highlighting its potential as a novel therapeutic target for breast cancer patients.