Objective: To investigate the potential biological function of ubiquitin-protein ligase E3A (UBE3A) in breast cancer cells through proteomics and bioinformatics methods. 
Methods: The triple-negative breast cancer MDA-MB-231 cells were transfected with shRNA-UBE3A sequences (UBE3A knock-down group) or scrambled shRNA sequences (control group), respectively. Then, the differentially expressed proteins between the two groups of cells were separated and identified by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization (MALDI-TOF-TOF-MS/MS); bioinformatics analyses of the differentially expressed proteins were performed using DAVID Functional Annotation and String online tools.
Results: Twenty-eight differentially expressed proteins were obtained and identified by 2-DE and MALDI-TOF-TOF-MS/MS, and 23 proteins were matched in DAVID database, in which, 4 were up-regulated, 24 were down-regulated in UBE3A knock-down group versus control group. Twenty-three proteins were recognized by DAVID database, in which, 23 (100%), 20 (87.7%) and 23 (100%) proteins could be annotated by biological pathway, cellular components and annotation of molecule functions especially, some of them were clearly related to the ubiquitin-proteasome system and glucose metabolism. String analysis showed that there were direct or indirect relations among the 23 proteins.
Conclusion: UBE3A may participate in regulation of the biological behaviors of breast cancer cells via the ubiquitin-proteasome system and glucose metabolism pathway.