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.

Identification of a ferroptosis-related gene pair biomarker with immune infiltration landscapes in ischemic stroke: a bioinformatics-based comprehensive study

“…Continuous variables were expressed as mean ± SD, and differences between two groups were compared using Student’s t-test for normally distributed variables and Mann–Whitney U test for abnormally distributed variables. Differential expression analysis was performed with the cut-off thresholds of P < 0.05 and |log 2 FC| > 0.58 or |FC| > 1.5, which was consistent with previously reported methods [ 36 , 37 ]. For each study, P < 0.05 was considered as a significant difference.…”

“…Using R’s “ limma (v3.42.2) ” package to identify differential expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) between IS and control samples. The P < 0.05, |log 2 fold change (FC)| > 0.58 or |FC| > 1.5 were selected as the cut-off thresholds, in accordance with previously reported methods [ 36 , 37 ]. Among DEmRNAs, we took the DEmRNAs that were overlapped with the ferroptosis-related genes as the differentially expressed ferroptosis-related genes (DEFRGs).…”

Macrophage polarization regulates intervertebral disc degeneration by modulating cell proliferation, inflammation mediator secretion, and extracellular matrix metabolism

“…Polo like kinase 1 (PLK 1) plays an important role in the regulation of the cytoskeleton network during mitosis (32), and li et al demonstrated PLK1 expression was decreased in NPCs of degenerative IVDs (33). In addition, CCNB1 is a member of cyclin family, which is responsible for cell proliferation and differentiation (34). Its elimination inhibits the proliferation of IVD cells, revealing that CCNB1 is an important regulator of the G2/M phase of NP cells (35).…”

Key LncRNAs Associated With Oxidative Stress Were Identified by GEO Database Data and Whole Blood Analysis of Intervertebral Disc Degeneration Patients

“…Usually called CD8+T cells are CTLs, its main function is to kill target cells. Recent studies have indicated that CD8 T cells in rat IDD models are more prone to apoptosis, and CD8 T cells play a role in the pathogenesis of IDD and apoptosis (Li et al, 2020a;Cao et al, 2021). T cells gamma delta (Tgd) is a unique group of lymphocytes that are often enriched on the surface of epithelial cells.…”