PDF(Pubmed)
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.
摘要：
腰背痛（LBP）是一个全球性的公共卫生问题。椎旁肌肉变性（PMD）被认为与LBP有关。越来越多的证据表明，microRNA（miRNA）-mRNA信号网络与疾病的病理生理学有关。研究表明，细胞死亡，氧化应激，炎症和免疫反应，和细胞外基质（ECM）代谢是PMD的发病机理；然而，miRNA-mRNA介导的PMD的病理过程仍然难以捉摸。RNA测序（RNA-seq）和单细胞RNA-seq（scRNA-seq）是揭示这些miRNA和基因表达变化背后的功能生物学的宝贵工具。使用scRNA-seq，我们发现在PMD过程中存在多个免疫细胞，揭示他们可能与PMD有牵连。此外,使用RNA-seq，我们鉴定了76个差异表达基因（DEG）和106个差异表达miRNA（DEM），其中IL-24和CCDC63是PMD中最高上调和下调的基因。综合生物信息学分析，包括维恩图，差异表达，功能富集，和蛋白质-蛋白质相互作用分析，然后进行鉴定六个与铁凋亡相关的DEGs，两个氧化应激相关的DEGs，十一个免疫相关的DEG，五个ECM相关DEG，其中AKR1C2/AKR1C3/SIRT1/ALB/IL-24属于炎症基因。此外，通过合并RNA-seq，预测67个DEM是25个关键DEG的上游miRNA，TargetScan,和mirDIP数据库。最后,使用Cytoscape软件和冲积图构建miRNA-基因网络.ROC曲线分析揭示了具有较高临床诊断价值的多个关键DEGs,提供诊断和治疗PMD疾病的新方法。
