Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Metab Brain Dis. 2022 Oct;37(7):2405-2415. doi: 10.1007/s11011-022-01015-3. Epub 2022 Jul 8.
Spinal cord injury (SCI) was a serious nerve injury, which involves complex genetic changes. This paper was intended to investigate the function and mechanism of differentially expressed genes in SCI. The three datasets GSE92657, GSE93561 and GSE189070 of SCI from GEO database were used to identify differentially expressed genes (DEGs). We identified the common DEGs in the three datasets GSE92657, GSE93561 and GSE189070 of SCI from GEO database. Next, a protein-protein interaction (PPI) network of DEGs was constructed. Subsequently, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were significantly enriched in immune response, inflammatory response. The expression level of immune-related genes (Arg1, Ccl12, Ccl2, Ifitm2, Ifitm3, and et al.) at different time points of SCI were analyzed in GSE189070 dataset. Next, differentially expressed miRNAs (DE-miRNAs) were identified in SCI compared with normal based on GSE158194 database. DE-miRNA and targeted immune-related genes were predicted by miRwalk, including miR-487b-5p targeted Ifitm3, miR-3072-5p targeted Ccl3, and et al. What's more, the miR-487b was identified and verified to be down-regulated in Lipopolysaccharide (LPS)-induced BV-2 cell model. Further, the miR-487b inhibited cell inflammation and apoptosis in LPS-induced BV2 cell by targeted Ifitm3. For the first time, our results revealed that miR-487b may play an important regulatory role in SCI by targeted Ifitm3 and provide further evidence for SCI research.
脊髓损伤 (SCI) 是一种严重的神经损伤,涉及复杂的遗传变化。本文旨在研究 SCI 差异表达基因的功能和机制。从 GEO 数据库中使用三个 SCI 数据集 GSE92657、GSE93561 和 GSE189070 来识别差异表达基因 (DEGs)。我们鉴定了 GSE92657、GSE93561 和 GSE189070 三个数据集的 SCI 中的共同 DEGs。接下来,构建了一个 DEG 的蛋白质-蛋白质相互作用 (PPI) 网络。随后,基因本体论 (GO) 和京都基因与基因组百科全书 (KEGG) 分析表明,DEGs 在免疫反应、炎症反应中显著富集。在 GSE189070 数据集分析了 SCI 不同时间点免疫相关基因(Arg1、Ccl12、Ccl2、Ifitm2、Ifitm3 等)的表达水平。接下来,基于 GSE158194 数据库,比较 SCI 与正常对照之间的差异表达 miRNA (DE-miRNA)。通过 miRwalk 预测 DE-miRNA 和靶向免疫相关基因,包括 miR-487b-5p 靶向 Ifitm3、miR-3072-5p 靶向 Ccl3 等。此外,还鉴定并验证了 miR-487b 在脂多糖 (LPS) 诱导的 BV-2 细胞模型中下调。进一步,miR-487b 通过靶向 Ifitm3 抑制 LPS 诱导的 BV2 细胞炎症和凋亡。首次表明,miR-487b 可能通过靶向 Ifitm3 在 SCI 中发挥重要调节作用,为 SCI 研究提供了进一步证据。