An Oxidative Stress-Related Gene Pair (CCNB1/ PKD1), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development

Abstract

Oxidative stress (OS) irreversibly affects the pathogenesis of intervertebral disc degeneration (IDD). Certain non-coding RNAs act as competitive endogenous RNAs (ceRNAs) that regulate IDD progression. Analyzing the signatures of oxidative stress-related gene (OSRG) pairs and regulatory ceRNA mechanisms and immune-infiltration patterns associated with IDD may enable researchers to distinguish IDD and reveal the underlying mechanisms. In this study, OSRGs were downloaded and identified using the Gene Expression Omnibus database. Functional-enrichment analysis revealed the involvement of oxidative stress-related pathways and processes, and a ceRNA network was generated. Differentially expressed oxidative stress-related genes (De-OSRGs) were used to construct De-OSRG pairs, which were screened, and candidate De-OSRG pairs were identified. Immune cell-related gene pairs were selected via immune-infiltration analysis. A potential long non-coding RNA-microRNA-mRNA axis was determined, and clinical values were assessed. Eighteen De-OSRGs were identified that were primarily related to intricate signal-transduction pathways, apoptosis-related biological processes, and multiple kinase-related molecular functions. A ceRNA network consisting of 653 long non-coding RNA-microRNA links and 42 mRNA-miRNA links was constructed. Three candidate De-OSRG pairs were screened out from 13 De-OSRG pairs. The abundances of resting memory CD4⁺ T cells, resting dendritic cells, and CD8⁺ T cells differed between the control and IDD groups. CD8⁺ T cell infiltration correlated negatively with cyclin B1 (CCNB1) expression and positively with protein kinase D1 (PKD1) expression. CCNB1-PKD1 was the only pair that was differentially expressed in IDD, was correlated with CD8⁺ T cells, and displayed better predictive accuracy compared to individual genes. The PKD1-miR-20b-5p-AP000797 and CCNB1-miR-212-3p-AC079834 axes may regulate IDD. Our findings indicate that the OSRG pair CCNB1-PKD1, which regulates oxidative stress during IDD development, is a robust signature for identifying IDD. This OSRG pair and increased infiltration of CD8⁺ T cells, which play important roles in IDD, were functionally associated. Thus, the OSRG pair CCNB1-PKD1 is promising target for treating IDD.

Keywords: competitive endogenous RNA; cyclin B1; differential expression; gene pair; immune infiltration; intervertebral disc degeneration; oxidative stress; protein kinase D1.