ABSTRACT
OBJECTIVE@#To explore the molecular mechanism underlying the inhibitory effects of aspirin against human breast cancer cell proliferation through bioinformatics analysis.@*METHODS@#Drug Bank 5.1.3 was searched to identify direct protein targets (DPTs) of aspirin, and the protein-protein interaction (PPI) network of the DPTs was constructed online using STRING and the signaling pathways involved were identified. The genetic alterations of 6 DPTs associated with human breast cancer was analyzed and visualized by cBio Portal and OncoPrint, respectively. The transcriptomic data of breast cancer and normal tissues were downloaded from TCGA database, and the overexpressed genes were analyzed by DECenter. The intersection between the genes associated with the DPTs obtained by STRING analysis and the differentially over-expressed genes in TCGA was determined to confirm the candidate DPTs as a potential target of aspirin, and GO functional enrichment analysis was performed using Gene Ontology. The potential targets of aspirin against the proliferation of human breast cancer cells were verified by Western blotting.@*RESULTS@#Eleven DPTs of aspirin were identified. KEGG pathway enrichment indicated that 6 genes (EDNRA, IKBKB, NFKB2, NFKBIA, PTGS2 and TP53) were associated with the occurrence and development of cancer. A total of 10 220 differentially expressed genes were identified from the TCGA database, and among them 4 genes (, , , ) were found to be the potential targets for aspirin. These genes were involved mostly in the regulation of cell cycle and cell division. Western blotting showed that aspirin could down-regulate the expression levels of several pivotal proteins that regulated cell cycle and cell division, including , , and .@*CONCLUSIONS@#, , and may be potential targets for aspirin to inhibit the proliferation of human breast cancer cells, by affecting the progress of cell cycle and cell division.
ABSTRACT
[Abstract ] Objective Bioinformatics provides a lot of valuable information for online prediction of new genes.In this study, we predicted the biological function of ubiquitin-conjugating enzyme 2S ( UBE2S) based on bioinformatics. Methods The UBE2S gene was screened and cloned from the cDNA library of human HepG2 cells.The relationship of the structure and function of UBE2S was explored based on the full-length cDNA library.MEGA5.05, CLUSTALW2 and SWISS-MODEL were used to study the phylogeny, conservation, and 3D structure of UBE2S. Results The UBE2S gene encoded a polypeptide of 241 residues with a predicted molec-ular weight of 23 770 and an isoelectric point of 8.81.The UBE2S protein contained no transmembrane locus and the probabilities of their functions of growth factors, cation channel and structural protein were 8.904, 0.313, and 0.291.The analysis of BLASTp showed that the isolated UBE2S had a 90-97%identity with the other species. Conclusion Analysis of the structure and function of the UBE2S protein can not only provide more information about its gene family but also pave the way for further experimental studies on the molecular mechanism of the consequent hepatocellular carcinoma.