Effects of UBE2T on Proliferation, Apoptosis, and Epithelial-Mesenchymal Transition of Breast Cancer Cells

ObjectiveTo investigate the expression of ubiquitin binding enzyme E2T (UBE2T) in breast cancer (BRCA) and its role and mechanism in the prognosis of BRCA patients. MethodsThe Tumor Genome Atlas (TCGA) database was used to analyze UBE2T expression in BRCA tissues, and the effects of UBE2T expression on disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier (KM) survival curve. In vitro, real-time quantitative PCR and Western blot were used to confirm the knock-down and overexpression efficiency, to analyze its effect on tumor cell biological behavior. The effect of UBE2T on cell epithelial–mesenchymal transition (EMT) was studied by Western blot. A xenograft tumor model was established to verify the effect of UBE2T knockdown on the growth of BRCA cells in vivo. ResultsThe UBE2T expression levels in BRCA and adjacent tissues were statistically different (P<0.001), and the expression was increased in tissues with distant metastasis or late stage (all P<0.05). The DFS and OS were decreased in the UBE2T high-level group (both P<0.05). UBE2T was highly expressed in MCF-7 and MDA-MB-231 cells and lowly expressed in MDA-MB-361 cells (all P<0.01). After UBE2T was silenced by shRNA, the proliferation ability of tumor cells significantly decreased, whereas it increased after UBE2T up-expression (all P<0.05). The apoptotic rates of MCF-7 and MDA-MB-231 cells in the silent groups were significantly higher than those in the shNC groups, while the apoptotic rates of MAD-MB-361 cells in the overexpression group decreased (all P<0.001). The mobility in the knockdown groups were lower than in the shNC groups, while the mobility in the overexpression group significantly increased (both P<0.01). The migration and invasion cells in the shUBE2T groups were lower than those in the shNC groups, and the migration and invasion cells in the UBE2T group were higher than those in the vector group (all P<0.01). Downregulation of UBE2T decreased the expression levels of N-cadherin, Snail, and Vimentin (all P<0.05) and increased that of E-cadherin; however, the result of UBE2T upregulation was opposite (all P<0.01). TIMER results showed that UBE2T was positively correlated with E-cadherin (P<0.001), N-cadherin (P=0.013), and Snail (P<0.001) and negatively correlated with Vimentin (P<0.001). In vivo experiments showed that downregulation of UBE2T slowed down the growth of transplanted tumors. ConclusionUBE2T is highly expressed in BRCA tissues and may affect the prognosis. UBE2T can promote the proliferation of BRCA cells, inhibit apoptosis, and increase the migration and invasion abilities by changing the expression levels of EMT-related proteins.