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.

Analysis of key genes and immune infiltration in ruptured intracranial aneurysms based on artificial neural networks and bioinformatics

“…It can be induced by tumor necrosis factor-α (TNF-α) and interferon-γ [13]. TNF-α upregulates NCF2 expression, promotes reactive oxygen species production, and activates MMPs and the p38 MAPK pathway, which further enhances the in ammatory response [14]. MMP9 is a member of the MMP family and is mainly involved in the reorganization and degradation of the extracellular matrix.…”

Transcriptomic Studies on Intracranial Aneurysms

“…It is easier to design a new study and to obtain blood samples than aneurysmal specimens. In this category of studies, only three out of nine studies used data from at least two datasets [ 86 , 87 , 88 ], and six analyses were based on a single dataset [ 89 , 90 , 91 , 92 , 93 , 94 ]. Analytical methods used did not significantly differ when compared to tissue-based studies.…”