Identifying the miRNA-gene networks contributes to exploring paravertebral muscle degeneration's underlying pathogenesis and therapy strategy

Abstract

Low back pain (LBP) is a worldwide problem with public health. Paravertebral muscle degeneration (PMD) is believed to be associated with LBP. Increasing evidence has demonstrated that microRNA (miRNA)-mRNA signaling networks have been implicated in the pathophysiology of diseases. Research suggests that cell death, oxidative stress, inflammatory and immune response, and extracellular matrix (ECM) metabolism are the pathogenesis of PMD; however, the miRNA-mRNA mediated the pathological process of PMD remains elusive. RNA sequencing (RNA-seq) and single cell RNA-seq (scRNA-seq) are invaluable tools for uncovering the functional biology underlying these miRNA and gene expression changes. Using scRNA-seq, we show that multiple immunocytes are presented during PMD, revealing that they may have been implicated with PMD. Additionally, using RNA-seq, we identified 76 differentially expressed genes (DEGs) and 106 differentially expressed miRNAs (DEMs), among which IL-24 and CCDC63 were the top upregulated and downregulated genes in PMD. Comprehensive bioinformatics analyses, including Venn diagrams, differential expression, functional enrichment, and protein-protein interaction analysis, were then conducted to identify six ferroptosis-related DEGs, two oxidative stress-related DEGs, eleven immunity-related DEGs, five ECM-related DEGs, among which AKR1C2/AKR1C3/SIRT1/ALB/IL-24 belong to inflammatory genes. Furthermore, 67 DEMs were predicted to be upstream miRNAs of 25 key DEGs by merging RNA-seq, TargetScan, and mirDIP databases. Finally, a miRNA-gene network was constructed using Cytoscape software and an alluvial plot. ROC curve analysis unveiled multiple key DEGs with the high clinical diagnostic value, providing novel approaches for diagnosing and treating PMD diseases.