Department of Neurosurgery, The Second Hospital of Jilin University, Changchun, 130021, China.
Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, 130000, China.
Mol Neurobiol. 2024 Dec;61(12):10901-10915. doi: 10.1007/s12035-024-04189-2. Epub 2024 May 29.
This study aims to elucidate the key regulatory molecules, specifically messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and microRNAs (miRNAs) and their roles in the development and progression of spinal cord injury (SCI). Expression profiles (GSE45006, GSE19890, and GSE125630) for SCI were sourced from the Gene Expression Omnibus (GEO) database. By comparing rats with SCI at various time points against those without SCI, we identified differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs), and miRNAs (DEmiRNAs). The GSE45006 dataset facilitated the production of DEmRNAs, which were then clustered using Mfuzz. Subsequently, we constructed a protein-protein interaction (PPI) network and anticipated interaction pairs between miRNA-mRNA and lncRNA-mRNA. These pairs were instrumental in forming a regulatory network involving lncRNA-miRNA-mRNA interactions. Additionally, we conducted functional enrichment studies on the DEmRNAs within these gene networks. A total of 2313 DEmRNAs were identified using the GSE45006 dataset, alongside 111 DEmiRNAs from GSE19890. From GSE125630, we extracted 154 DElncRNAs and 2322 DEmRNAs. Our analysis revealed 294 up-regulated DEmRNAs, grouped into the up-cluster, and 407 down-regulated DEmRNAs, forming the down-cluster. Key hub genes in the PPI network, such as Rhof, Vav1, Lyz2, Rab3a, Lyn, Cyfip1, Gns, and Nckap1l, were identified. Additionally, the study successfully constructed a competing endogenous RNA (ceRNA) network, revealing 55 unique lncRNA-miRNA-mRNA link pairs. Our research established a ceRNA network associated with SCI, identifying several critical lncRNA-miRNA-mRNA connection pairs integral to the disease's onset and progression. Notably, significant associations, including the AABR07041411.1-miR-125a-5p-Slc4a7 and the Smg1-rno-miR-331-3p-Tlr4 pairs, were observed to exert a significant influence within this biological context.
本研究旨在阐明关键调控分子,特别是信使 RNA(mRNA)、长非编码 RNA(lncRNA)和 microRNA(miRNA)及其在脊髓损伤(SCI)发生和进展中的作用。从基因表达综合数据库(GEO)中获取了 SCI 的表达谱(GSE45006、GSE19890 和 GSE125630)。通过比较不同时间点 SCI 大鼠与未 SCI 大鼠,我们鉴定了差异表达的 mRNAs(DEmRNAs)、lncRNAs(DElncRNAs)和 miRNAs(DEmiRNAs)。GSE45006 数据集有助于生成 DEmRNAs,然后使用 Mfuzz 对其进行聚类。随后,我们构建了一个蛋白质-蛋白质相互作用(PPI)网络,并预测了 miRNA-mRNA 和 lncRNA-mRNA 之间的相互作用对。这些对在形成涉及 lncRNA-miRNA-mRNA 相互作用的调控网络方面发挥了重要作用。此外,我们对这些基因网络中的 DEmRNAs 进行了功能富集研究。使用 GSE45006 数据集鉴定了 2313 个 DEmRNAs,从 GSE19890 中提取了 111 个 DEmiRNAs。从 GSE125630 中,我们提取了 154 个 DElncRNAs 和 2322 个 DEmRNAs。我们的分析显示 294 个上调的 DEmRNAs,分为上调簇,和 407 个下调的 DEmRNAs,形成下调簇。在 PPI 网络中的关键枢纽基因,如 Rhof、Vav1、Lyz2、Rab3a、Lyn、Cyfip1、Gns 和 Nckap1l 等被鉴定出来。此外,该研究还成功构建了一个竞争性内源 RNA(ceRNA)网络,揭示了 55 个独特的 lncRNA-miRNA-mRNA 连接对。我们的研究建立了一个与 SCI 相关的 ceRNA 网络,鉴定了几个关键的 lncRNA-miRNA-mRNA 连接对,这些连接对对疾病的发生和发展至关重要。值得注意的是,在这个生物学背景下,观察到了显著的关联,包括 AABR07041411.1-miR-125a-5p-Slc4a7 和 Smg1-rno-miR-331-3p-Tlr4 对的显著影响。