美图再中刊!《Heliyon》探索椎旁肌退化的潜在发病机制相关

发布时间：2024-05-16 11:12:37

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期刊：Heliyon（IF：4）

文章名:《Identifying the miRNA-gene networks contributes to exploring paravertebral muscle degeneration’s underlying pathogenesis and therapy strategy》

原文链接:https://doi.org/10.1016/j.heliyon.2024.e30517

摘要（百度翻译）：

腰痛（LBP）是一个全球性的公共卫生问题。椎旁肌退化（PMD）被认为与LBP有关。越来越多的证据表明，微小RNA（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、炎症和免疫反应以及细胞外基质（ECM）代谢是PMD的发病机制；然而，miRNA-mRNA介导PMD的病理过程仍然难以捉摸。RNA测序（RNA-seq）和单细胞RNA-seq是揭示功能生物学的宝贵工具这些miRNA和基因表达变化的基础。使用scRNA-seq，我们发现在PMD期间存在多个免疫细胞，这表明它们可能与PMD有关。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中上调和下调最多的基因。然后进行全面的生物信息学分析，包括Venn图、差异表达、功能富集和蛋白质-蛋白质相互作用分析，以鉴定6个脱铁相关的DEG、2个氧化应激相关的DEGs、11个免疫相关的DEG，AKR1C3/SIRT1/ALB/IL-24属于炎症基因。此外，通过合并RNA-seq、TargetScan和mirDIP数据库，预测67个DEM是25个关键DEG的上游miRNA。最后，使用Cytoscape软件和冲积图构建了miRNA基因网络。ROC曲线分析揭示了多个具有较高临床诊断价值的关键DEG，为PMD疾病的诊断和治疗提供了新的途径。

Abstract

Low back pain (LBP) is a worldwide problem with public health. Paravertebral muscle degen eration (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 pre dicted 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.

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