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

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Intervertebral disc degeneration (IVDD) is a major cause of low back pain, but its molecular underpinnings are not fully understood.
• Ubiquitin-conjugating enzymes (E2 enzymes) are crucial for protein degradation and cellular homeostasis, yet their role in IVDD is largely unexamined.

Purpose of the Study:

• To identify key E2 enzymes involved in IVDD pathogenesis.
• To investigate the expression and potential role of UBE2Q2 in intervertebral disc degeneration.

Main Methods:

• Differential gene expression analysis of public datasets (GEO: GSE70362, GSE23130).
• Weighted Gene Co-expression Network Analysis (WGCNA) to identify hub genes.
• Single-cell RNA sequencing (GSE251686) to analyze UBE2Q2 expression in disc cell subpopulations.
• Validation using qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence in human and rat IVDD models.

Main Results:

• Bioinformatic analyses revealed significant upregulation of UBE2Q2 in IVDD datasets.
• WGCNA identified UBE2Q2 as a central hub gene associated with degeneration.
• Single-cell data and experimental validation confirmed elevated UBE2Q2 mRNA and protein levels in degenerated nucleus pulposus (NP) tissues and cells.

Conclusions:

• UBE2Q2 is significantly upregulated in intervertebral disc degeneration.
• UBE2Q2 is identified as a potential biomarker and a novel molecular target for IVDD.
• This study provides a basis for further research into UBE2Q2's functional and mechanistic roles in IVDD.