Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, 330006, 1 Minde Road, East Laker District, Nanchang, China.
Institute of Orthopedics of Jiangxi Province, Jiangxi 330006, 1 Minde Road, East Laker District, Nanchang, China.
Comput Math Methods Med. 2023 Jan 19;2023:6033020. doi: 10.1155/2023/6033020. eCollection 2023.
Spinal cord injury (SCI) is a serious disorder of the central nervous system with a high disability rate. Long noncoding RNAs (lncRNAs) are reported to mediate many biological processes. The aim of this study was to explore lncRNA and mRNA expression profiles and functional networks after SCI. Differentially expressed genes between SCI model rats and sham controls were identified by microarray assays and analyzed by functional enrichment. Key lncRNAs were identified using a support vector machine- (SVM-) recursive feature elimination (RFE) algorithm. A trans and cis regulation model was used to analyze the regulatory relationships between lncRNAs and their targets. An lncRNA-related ceRNA network was established. We identified 5465 differentially expressed lncRNAs (DE lncRNAs) and 8366 differentially expressed mRNAs (DE mRNAs) in the SCI group compared with the sham group (fold change > 2.0, < 0.05). Four genes were confirmed by qRT-PCR which were consistent with the microarray data. GSEA analysis showed that most marked changes occurred in pathways related to immune inflammation and nerve cell function, including cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and GABAergic synapse. Enrichment analysis identified 30 signaling pathways, including those associated with immune inflammation response. A total of 40 key lncRNAs were identified using the SVM-RFE algorithm. A key lncRNA-mRNAs coexpression network was generated for 230 951 lncRNA-mRNA pairs with half showing positive correlations. Several key DE lncRNAs were predicted to have "cis"- or "trans"-regulated target genes. The transcription factors, Sp1, JUN, and SOX10, may regulate the interaction between XR_001837123.1 and ETS 1. In addition, five pairs of ceRNA regulatory sequences were constructed. Many mRNAs and lncRNAs were found to be dysregulated after SCI. Bioinformatic analysis showed that DE lncRNAs may play crucial roles in SCI. It is anticipated that these findings will provide new insights into the underlying mechanisms and potential therapeutic targets for SCI.
脊髓损伤 (SCI) 是一种中枢神经系统的严重疾病，其致残率很高。长链非编码 RNA (lncRNA) 被报道介导许多生物过程。本研究旨在探讨 SCI 后 lncRNA 和 mRNA 的表达谱和功能网络。通过微阵列分析鉴定 SCI 模型大鼠与假手术对照之间差异表达的基因，并进行功能富集分析。使用支持向量机-（SVM-）递归特征消除（RFE）算法鉴定关键 lncRNA。使用顺式和反式调控模型分析 lncRNA 与其靶基因之间的调控关系。建立 lncRNA 相关的 ceRNA 网络。与假手术组相比，SCI 组中鉴定出 5465 个差异表达的 lncRNA (DE lncRNA) 和 8366 个差异表达的 mRNA (DE mRNA) (fold change > 2.0, < 0.05)。通过 qRT-PCR 验证了 4 个基因，与微阵列数据一致。GSEA 分析显示，大多数明显变化发生在与免疫炎症和神经细胞功能相关的途径中，包括细胞因子-细胞因子受体相互作用、神经活性配体-受体相互作用和 GABA 能突触。富集分析确定了 30 个信号通路，包括与免疫炎症反应相关的通路。使用 SVM-RFE 算法鉴定出 40 个关键 lncRNA。生成了包含 230951 个 lncRNA-mRNA 对的关键 lncRNA-mRNAs 共表达网络，其中一半显示出正相关。一些关键的 DE lncRNA 被预测具有“顺式”或“反式”调控靶基因。转录因子 Sp1、JUN 和 SOX10 可能调节 XR_001837123.1 和 ETS 1 之间的相互作用。此外，构建了五对 ceRNA 调控序列。许多 mRNAs 和 lncRNAs 在 SCI 后失调。生物信息学分析表明，DE lncRNA 可能在 SCI 中发挥关键作用。预计这些发现将为 SCI 的潜在机制和治疗靶点提供新的见解。
