Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods.

Abstract

The present study aimed to explore potential molecular targets and gain further insights into the mechanism of intervertebral disc degeneration (IDD) progression. Microarray datasets of GSE19943, GSE15227 and GSE34095 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in 3 IDD specimens compared with 3 controls in GSE34095, DEGs in 7 grade III and 3 grade IV samples compared with 5 grade II samples in GSE19943, and differentially expressed miRNAs in 3 degenerated samples compared with 3 controls in GSE15227 were screened. Grade III‑ and IV‑specific networks were constructed and grade‑specific genes were extracted. The network features were analyzed, followed by Gene Ontology (GO) enrichment analysis and pathway enrichment analysis of grade‑specific genes and DEGs identified in GSE34095. Furthermore, miRNA‑pathway interactions were analyzed using Fisher's exact test. Tumor protein p53 (TP53) was a hub gene in the grade III‑specific network and ubiquitin C (UBC) was identified to be a hub gene in the grade IV‑specific network. Six significant features were identified by grade‑specific network topology analysis. Grade‑specific genes and DEGs were involved in different GO terms and pathways. Differentially expressed miRNAs were identified to participate in 35 pathways, among which 6 pathways were significantly enriched by DEGs, including apoptosis. The present study identified that key genes (TP53 and UBC) and miR‑129‑5p may participate in the mechanism of IDD progression. Thus, they may be potential therapeutic targets for IDD.