Integrated Multi-Omics Analysis and Experimental Validation Identify UBE2Q2 as a Candidate Molecule Target in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a primary cause of low back pain, with its molecular mechanisms remaining incompletely understood. Ubiquitin-conjugating enzymes (E2 enzymes) play critical roles in protein degradation and maintenance of cellular homeostasis, yet their expression profiles and functional significance in IVDD remain largely unexplored. Using Gene Expression Omnibus (GEO) datasets (GSE70362 and GSE23130), we performed differential expression analysis, intersected with ubiquitination-related genes, and applied weighted gene co-expression network analysis (WGCNA) to identify key E2 enzymes in IVDD. Single-cell RNA sequencing (GSE251686) characterized UBE2Q2 expression in intervertebral disc cell subpopulations. qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence validated UBE2Q2 expression in human degenerated nucleus pulposus (NP) tissues and in vitro rat NP cell degeneration models. Bioinformatics analyses showed significant UBE2Q2 upregulation in IVDD, with WGCNA identifying it as a hub gene closely associated with degeneration. Consistently, single-cell data confirmed predominant UBE2Q2 expression in NP cells, with markedly higher levels in IVDD (p < 0.05). Moreover, experimental validation consistently demonstrated elevated UBE2Q2 mRNA and protein in degenerated human NP tissues and rat models, with stronger immunohistochemical and immunofluorescent signals in degenerated samples (p < 0.05). This study represents the first identification of UBE2Q2 as a potential biomarker and a new molecular target for IVDD, thereby providing a foundation for future functional and mechanistic investigations.