Department of Neurosurgery, Zhejiang Provincial Hospital of Traditional Chinese Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.
Mol Med Rep. 2020 Dec;22(6):4541-4550. doi: 10.3892/mmr.2020.11540. Epub 2020 Sep 25.
Ruptured intracranial aneurysm (IA)‑induced subarachnoid hemorrhage (SAH) triggers a series of immune responses and inflammation in the brain and body. The present study was conducted to identify additional circulating biomarkers that may serve as potential therapeutic targets for SAH‑induced inflammation. Differentially expressed (DE) long non‑coding RNAs (lncRNAs; DElncRNAs) and genes (DEGs) in the peripheral blood mononuclear cells between patients with IA rupture‑induced SAH and healthy controls were identified in the GSE36791 dataset. DEGs were used for weighted gene co‑expression network analysis (WGCNA), and SAH‑associated WGCNA modules were identified. Subsequently, an lncRNA‑mRNA regulatory network was constructed using the DEGs in SAH‑associated WGCNA modules. A total of 25 DElncRNAs and 1,979 DEGs were screened from patients with IA‑induced SAH in the GSE36791 dataset compared with the controls. A total of 11 WGCNA modules, including four upregulated modules significantly associated with IA rupture‑induced SAH were obtained. The DEGs in the SAH‑associated modules were associated with Gene Ontology biological processes such as 'regulation of programmed cell death', 'apoptosis' and 'immune response'. The subsequent lncRNA‑mRNA regulatory network included seven upregulated lncRNAs [HCG27, ZNFX1 antisense RNA 1, long intergenic non‑protein coding RNA (LINC)00265, murine retrovirus integration site 1 homolog‑antisense RNA 1, cytochrome P450 1B1‑AS1, LINC01347 and LINC02193] and 375 DEGs. Functional enrichment analysis and screening in the Comparative Toxicogenomics Database demonstrated that SAH‑associated DEGs, including neutrophil cytosolic factor (NCF)2 and NCF4, were enriched in 'chemokine signaling pathway' (hsa04062), 'leukocyte transendothelial migration' (hsa04670) and 'Fc gamma R‑mediated phagocytosis' (hsa04666). The upregulated lncRNAs and genes, including NCF2 and NCF4, in patients with IA rupture‑induced SAH indicated their respective potentials as anti‑inflammatory therapeutic targets.
颅内破裂动脉瘤（IA）引起的蛛网膜下腔出血（SAH）会在大脑和身体中引发一系列免疫反应和炎症。本研究旨在确定其他可能作为 SAH 诱导炎症的潜在治疗靶点的循环生物标志物。在 GSE36791 数据集，鉴定了患者外周血单核细胞中与 IA 破裂诱导的 SAH 相关的差异表达长非编码 RNA（lncRNA；DElncRNA）和基因（DEGs）。使用 DEGs 进行加权基因共表达网络分析（WGCNA），并鉴定与 SAH 相关的 WGCNA 模块。随后，使用与 SAH 相关的 WGCNA 模块中的 DEGs 构建 lncRNA-mRNA 调控网络。与对照组相比，从 GSE36791 数据集中筛选出 25 个 DElncRNA 和 1979 个 DEG。获得了 11 个 WGCNA 模块，包括 4 个与 IA 破裂诱导的 SAH 显著相关的上调模块。SAH 相关模块中的 DEGs 与基因本体论生物过程有关，如“程序性细胞死亡的调节”、“细胞凋亡”和“免疫反应”。随后的 lncRNA-mRNA 调控网络包括 7 个上调的 lncRNA[HCG27、ZNFX1 反义 RNA1、长非蛋白编码 RNA（LINC）00265、鼠逆转录病毒整合位点 1 同源反义 RNA1、细胞色素 P450 1B1-AS1、LINC01347 和 LINC02193]和 375 个 DEG。比较毒理学基因组数据库中的功能富集分析和筛选表明，包括中性粒细胞胞质因子（NCF）2 和 NCF4 在内的与 SAH 相关的 DEG 富集于“趋化因子信号通路”（hsa04062）、“白细胞跨内皮迁移”（hsa04670）和“Fc 伽马 R 介导的吞噬作用”（hsa04666）。IA 破裂诱导的 SAH 患者中上调的 lncRNA 和基因，包括 NCF2 和 NCF4，表明它们各自作为抗炎治疗靶点的潜力。
