Department of Neurology, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130021, Jilin, China.
BMC Neurol. 2021 May 14;21(1):197. doi: 10.1186/s12883-021-02156-1.
This study was performed to identify genes and lncRNAs involved in the pathogenesis of subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysm (RIA).
Microarray GSE36791 was downloaded from Gene Expression Omnibus (GEO) database followed by the identification of significantly different expressed RNAs (DERs, including lncRNA and mRNA) between patients with SAH and healthy individuals. Then, the functional analyses of DEmRNAs were conducted and weighted gene co-expression network analysis (WGCNA) was also performed to extract the modules associated with SAH. Following, the lncRNA-mRNA co-expression network was constructed and the gene set enrichment analysis (GSEA) was performed to screen key RNA biomarkers involved in the pathogenesis of SAH from RIA. We also verified the results in a bigger dataset GSE7337.
Totally, 561 DERs, including 25 DElncRNAs and 536 DEmRNAs, were identified. Functional analysis revealed that the DEmRNAs were mainly associated with immune response-associated GO-BP terms and KEGG pathways. Moreover, there were 6 modules significantly positive-correlated with SAH. The lncRNA-mRNA co-expression network contained 2 lncRNAs (LINC00265 and LINC00937) and 169 mRNAs. The GSEA analysis showed that these two lncRNAs were associated with three pathways (cytokine-cytokine receptor interaction, neurotrophin signaling pathway, and apoptosis). Additionally, IRAK3 and NFKBIA involved in the neurotrophin signaling pathway and apoptosis while IL1R2, IL18RAP and IL18R1 was associated with cytokine-cytokine receptor interaction pathway. The expression levels of these genes have the same trend in GSE36791 and GSE7337.
LINC00265 and LINC00937 may be implicated with the pathogenesis of SAH from RIA. They were involved in three important regulatory pathways. 5 mRNAs played important roles in the three pathways.
本研究旨在从颅内破裂动脉瘤（RIA）中识别蛛网膜下腔出血（SAH）发病机制相关的基因和长链非编码 RNA（lncRNA）。
从基因表达综合数据库（GEO）下载微阵列 GSE36791，鉴定 SAH 患者与健康个体之间差异表达的 RNA（DER，包括 lncRNA 和 mRNA）。然后，进行 DEmRNAs 的功能分析，并进行加权基因共表达网络分析（WGCNA）以提取与 SAH 相关的模块。随后构建 lncRNA-mRNA 共表达网络，并进行基因集富集分析（GSEA），以筛选与 RIA 所致 SAH 发病机制相关的关键 RNA 生物标志物。我们还在更大的数据集 GSE7337 中验证了结果。
共鉴定出 561 个 DER，包括 25 个 DElncRNA 和 536 个 DEmRNA。功能分析表明，DEmRNAs 主要与免疫反应相关的 GO-BP 术语和 KEGG 途径相关。此外，有 6 个模块与 SAH 呈显著正相关。lncRNA-mRNA 共表达网络包含 2 个 lncRNA（LINC00265 和 LINC00937）和 169 个 mRNA。GSEA 分析表明，这两个 lncRNA 与三个途径（细胞因子-细胞因子受体相互作用、神经营养因子信号通路和细胞凋亡）相关。此外，IRAK3 和 NFKBIA 参与神经营养因子信号通路和细胞凋亡，而 IL1R2、IL18RAP 和 IL18R1 与细胞因子-细胞因子受体相互作用途径相关。这些基因在 GSE36791 和 GSE7337 中的表达水平具有相同的趋势。
LINC00265 和 LINC00937 可能与 RIA 所致 SAH 的发病机制有关。它们参与了三个重要的调控途径。5 个 mRNA 在这三个途径中发挥重要作用。
