Identification of key genes and potential mechanisms based on the autophagy regulatory network in intervertebral disc degeneration

Abstract

Intervertebral disc degeneration (IDD) is a common musculoskeletal disease that develops with increasing age. However, the exact occurrence and progression of IDD remains unclear. Gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) repository. The NCBI GEO2R analysis tool was used to identify differentially expressed genes. The protein-protein interaction (PPI) network was predicted using the STRING website and visualized using the Cytoscape software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to enrich GO terms and signaling pathways using the Metascape database. To identify potential upstream miRNA targets of these differentially expressed genes, the mRNA-miRNA interaction networks were predicted by Network Analyst database. To identify the 2 key genes with significant differences among the 10 hub genes, the GraphPad Prism Tool and GeneCards database were used for analysis. 22 genes were identified. A PPI network was constructed and the other 30 related genes were deduced. GO and Kyoto Encyclopedia of Genes and Genomes enrichment networks indicated extracellular matrix organization, collagen-containing extracellular matrix and extracellular matrix structural constituent in extracellular matrix (ECM) regulation in IDD. The mRNA-miRNA interaction networks suggested that many miRNAs could regulate autophagy-related genes individually and collectively. The GraphPad Prism Tool and GeneCards database analysis results suggested that 2 hub genes were involved in IDD. Our results revealed that the role of ECM could be a regulatory mechanism in IDD and that these ECM-related genes might be targets for the intervention of IDD.