Identifying hub genes and potential mechanisms associated with senescence in human annulus cells by gene expression profiling and bioinformatics analysis

Abstract

The aim of the present study was to reveal the potential hub genes and regulatory mechanisms associated with senescence in human annulus cells by analyzing microarray data using bioinformatics. The gene expression dataset GSE17077, of senescent and non-senescent annulus cells obtained from patients with disc degenerative diseases (DDD), was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified. Functional and pathway annotations were performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms, respectively. Web-based Gene Set Analysis Toolkit and Chip Enrichment Analysis were used to identify key transcription factors (TFs). A protein-protein interaction (PPI) network was constructed to analyze the hub genes associated with senescence in DDD. A total of 667 DEGs were screened, including 368 up- and 299 down-regulated genes. These DEGs were enriched in phosphorylation, regulation of apoptosis and regulation of programmed cell death. In addition, DEGs were involved in axon guidance, natural killer cell-mediated cytotoxicity, purine metabolism and the mitogen-activated protein kinase (MAPK) signaling pathway. The TFs activator protein 1(AP1), specificity protein 1 and aryl hydrocarbon receptor may serve regulatory roles in gene expression in senescent cells. Certain key target genes of TFs, including heat shock protein 90 (HSP90) and C-X-C motif chemokine 5(CXCL5), within the DEGs were revealed to have a high connectivity degree by PPI analysis. The results of the present study indicated that the MAPK-regulated AP1 pathway may contribute to senescence-associated disc degeneration. The DEGs, including HSP90 and CXCL5, with a high degree of connectivity may be potential targets for future investigations into molecular biomarkers.