Zhang Yuxin, Zhang Dahe, Jiao Xin, Yue Xiaokun, Cai Bin, Lu Shenji, Xu Renjie
Department of Rehabilitation Medicine, Fengcheng branch, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China.
Heliyon. 2024 Apr 25;10(9):e30336. doi: 10.1016/j.heliyon.2024.e30336. eCollection 2024 May 15.
Adults with spinal cord injury (SCI), a destructive neurological injury, have a significantly higher incidence of osteoarthritis (OA), a highly prevalent chronic joint disorder. This study aimed to dissect the neuroimmune-related regulatory mechanisms of SCI and OA using bioinformatics analysis. Using microarray data from the Gene Expression Omnibus database, differentially expressed genes (DEGs) were screened between SCI and sham samples and between OA and control samples. Common DEGs were used to construct a protein-protein interaction (PPI) network. Weighted gene co-expression network analysis (WGCNA) was used to mine SCI- and OA-related modules. Shared miRNAs were identified, and target genes were predicted using the Human MicroRNA Disease Database (HMDD) database. A miRNA-gene-pathway regulatory network was constructed with overlapping genes, miRNAs, and significantly enriched pathways. Finally, the expression of the identified genes and miRNAs was verified using RT-qPCR. In both the SCI and OA groups, 185 common DEGs were identified, and three hub clusters were obtained from the PPI network. WGCNA revealed three SCI-related modules and two OA-related modules. There were 43 overlapping genes between the PPI network clusters and the WGCNA network modules. Seventeen miRNAs shared between patients with SCI and OA were identified. A regulatory network consisting of five genes, six miRNAs, and six signaling pathways was constructed. Upregulation of , , , and , while lower levels of miR-125b-5p, miR-130a-3p, miR-16-5p, miR-204-5p, and miR-204-3p in both SCI and OA were successfully verified using RT-qPCR. Our study suggests that a miRNA-gene-pathway network is implicated in the neuroimmune-related regulatory mechanisms of SCI and OA. , , , and , and their related miRNAs (miR-125b-5p, miR-130a-3p, miR-16-5p, miR-204-5p, and miR-204-3p) may serve as promising biomarkers and candidate therapeutic targets for SCI and OA.
脊髓损伤（SCI）是一种具有破坏性的神经损伤，患有SCI的成年人患骨关节炎（OA）的几率显著更高，OA是一种非常普遍的慢性关节疾病。本研究旨在通过生物信息学分析剖析SCI与OA的神经免疫相关调控机制。利用基因表达综合数据库中的微阵列数据，在SCI样本与假手术样本之间以及OA样本与对照样本之间筛选差异表达基因（DEG）。使用共同的DEG构建蛋白质-蛋白质相互作用（PPI）网络。采用加权基因共表达网络分析（WGCNA）挖掘与SCI和OA相关的模块。鉴定共享的微小RNA（miRNA），并使用人类微小RNA疾病数据库（HMDD）预测靶基因。用重叠基因、miRNA和显著富集的通路构建miRNA-基因-通路调控网络。最后，使用逆转录定量聚合酶链反应（RT-qPCR）验证所鉴定基因和miRNA的表达。在SCI组和OA组中均鉴定出185个共同的DEG，并从PPI网络中获得三个枢纽簇。WGCNA揭示了三个与SCI相关的模块和两个与OA相关的模块。PPI网络簇与WGCNA网络模块之间有43个重叠基因。鉴定出SCI患者和OA患者之间共享的17种miRNA。构建了一个由五个基因、六个miRNA和六个信号通路组成的调控网络。通过RT-qPCR成功验证了SCI和OA中 、 、 、 的上调，以及miR-125b-5p、miR-130a-3p、miR-16-5p、miR-204-5p和miR-204-3p的较低水平。我们的研究表明，一个miRNA-基因-通路网络参与了SCI和OA的神经免疫相关调控机制。 、 、 、 及其相关miRNA（miR-125b-5p、miR-130a-3p、miR-16-5p、miR-204-5p和miR-204-3p）可能作为SCI和OA有前景的生物标志物和候选治疗靶点。
