Dataset Information

Identification of upregulated NF-κB inhibitor alpha and IRAK3 targeting lncRNA following intracranial aneurysm rupture-induced subarachnoid hemorrhage.

ABSTRACT:

Background

This study was performed to identify genes and lncRNAs involved in the pathogenesis of subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysm (RIA).

Methods

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.

Results

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.

Conclusion

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.

SUBMITTER: Leng W

PROVIDER: S-EPMC8120017 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.

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