Identification of inflammation‑associated circulating long non‑coding RNAs and genes in intracranial aneurysm rupture‑induced subarachnoid hemorrhage.

Abstract

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.