Abstract
Intervertebral disc degeneration (IVDD) is a prevalent musculoskeletal disorder characterized by the deterioration of nucleus pulposus (NP) cells, leading to symptoms that significantly impact patients' quality of life. Understanding the molecular mechanisms underlying IVDD is crucial for developing effective therapeutic strategies. In this study, we employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify key module eigengenes (MEs) from the GSE124272 dataset, followed by differential gene expression analysis to identify differentially expressed genes (DEGs). Functional enrichment analysis indicated that MEs were linked to lipid metabolism and immune response, while DEGs were related to immune response and cell proliferation. By intersecting MEs, DEGs, and ferroptosis-related genes, we identified six hub genes (ACSL1, BACH1, CBS, CP, AKR1C1, AKR1C3). Consensus clustering analysis categorized samples into two immune-related subgroups, C1 and C2, with subsequent single-sample Gene Set Enrichment Analysis (ssGSEA) revealing distinct immune scores between the two subgroups. Notably, ACSL1 exhibited the highest correlation with immune cell infiltration, and its expression was significantly upregulated in the C1 subgroup, correlating with elevated immune scores. In vitro experiments validated increased expression of ACSL1 in the IL-1β-induced degenerative NP cell model, and silencing of ACSL1 resulted in improvements in cell viability, apoptosis, mitochondrial membrane potential, intracellular Fe2+, MDA, and GSH levels. Collectively, these findings suggest that ACSL1 serves as a biomarker for IVDD and may represent a potential therapeutic target for IVDD treatment.