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.

Inflammation and immune cell abnormalities in intracranial aneurysm subarachnoid hemorrhage (SAH): Relevant signaling pathways and therapeutic strategies

“…TLR-4 activation potentially acts as a costimulatory molecule for T-cell activation, where the cytokines IFN-γ and IL-1 participate in this process within the brain immune microenvironment and constitute the neuroinflammation ( 253 – 255 ). NF-κB is a putative inflammation regulator in multiple pro-inflammatory functions ( 256 ), which influences the DNA transcription and immune response in aneurysm SAH ( 171 ). Pro-inflammatory factors TNF-α, IL-1β, COX, and MMP-9 gene expressions were reported to be regulated by NF-κB ( 119 , 257 ).…”

“…The aneurysm wall is characterized by brain immune cell population alteration, such as NKs, T cells, mast cells, and macrophages ( 258 ). On the other hand, the expression of NF-κB inhibitor gene NFKBIA in SAH patients has an anti-inflammatory effect and is associated with apoptosis and neurotrophin signaling ( 171 ). Activated microglia were attributed to roles as antigen-presenting cells and respond to TLR-4, thus shaping the adaptive immune response in the neuroinflammation ( 259 ).…”

LINC00937 acts bi-function in oral squamous cell carcinoma cell growth and immune cell infiltration regulated FGR/IL10RA axis

“…Our data showed that LINC00937 was rstly up-regulated in OSCC tissues and then associated with poor prognosis and well AUC areas in OSCC development. Aberrant expressions of LINC00937 have been detected in several human carcinomas, such as keloid broblast (19), subarachnoid hemorrhage (14), as well as cutaneous melanoma (12). However, there is no evidence indicated that LINC00937 might put to use crucial roles in human tumors, especially OSCC.…”

“…For instance, LINC00937 can inhibit keloid broblast growth and EMD(extracellular matrix deposition) via miR-28-5p/MC1R axis (13). Recently, LINC00937 can increase the function of NF-κB inhibitor-α, and direct target IRAK3 expression suppressed subarachnoid hemorrhage (14). However, the clinical value and natural part of LINC00937 in OSCC have no investigated.…”

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.…”