Identification of common pathway and hub genes in the degeneration of both annulus fibrosus and nucleus pulposus in intervertebral disc.

Abstract

Purpose: This study aimed to identify the common pathways and hub genes related to oxidative stress (OS) and autophagy of both annulus fibrosus (AF) and nucleus pulposus (NP) in intervertebral disc degeneration (IDD) based on the data obtained from the Gene Expression Omnibus (GEO) database.

Methods: The Gene expression data for human intervertebral discs was obtained from the GEO database, including the AF and NP of both non-degenerated disc and degenerated disc. The differentially expressed genes (DEGs) were identified using the limma package in R language. DEGs related to OS and autophagy were obtained using Gene Ontology (GO) database. Analyses of the GO, signaling pathways, protein-protein interaction (PPI) networks, and hub genes were performed using AnnotationDbi package, DAVID, GSEA, STRING database, and Cytoscape software, respectively. Finally, the online tool of NetworkAnalyst and the Drug Signatures database (DSigDB) were used to screen for transcriptional factors and potential drugs of the hub genes.

Results: There were 908 genes associated with OS and autophagy found. A total of 52 DEGs were identified, included five upregulated and 47 downregulated genes. These DEGs were mainly involved in mTOR signaling pathway and the NOD-like receptor signaling pathway. The top 10 hub genes were CAT, GAPDH, PRDX1, PRDX4, TLR4, GPX7, GPX8, MSRA, RPTOR, GABARAPL1. Besides, FOXC1, PPARG, RUNX2, JUN, and YY1 were identified as the key regulatory factors of hub genes. L-cysteine, oleanolic acid, and berberine were potential therapeutic agents for the treatment of IDD.

Conclusions: Common hub genes, signaling pathways, transcription factors, and potential drugs associated with OS and autophagy were identified, which provides significant basis for further mechanism research and drug screening of IDD.