Identification of key genes, transcription factors and microRNAs involved in intracranial aneurysm

Abstract

Intracranial aneurysm (IA) is a devastating disease, the pathogenesis of which remains to be elucidated. The present study aimed to determine the molecular mechanism of IA and to identify potential therapeutic targets using bioinformatics analysis. The GSE54083 dataset, which includes data from patients with ruptured IA and superficial temporal artery controls, was downloaded from the Gene Expression Omnibus, and differentially expressed genes (DEGs) were identified in the ruptured IA samples using the limma package in R. Subsequently, the Database for Annotation, Visualization and Integrated Discovery software was used to perform function and pathway enrichment analyses and the Search Tool for the Retrieval of Interacting Genes database was used to construct the protein-protein interaction (PPI) network. Then, microRNA (miRNA) target and transcription factor (TF) target pairs were identified using the miR2Disease, MiRwalk2, ITFP and TRANSFAC databases. Finally, an integrated network of TF-target-miRNAs was constructed using Cytoscape. A total of 402 upregulated DEGs and 375 downregulated DEGs were identified from the ruptured IA samples compared with the superficial temporal artery samples. The majority of the upregulated DEGs were significantly enriched in the immune system development category, including CD40 ligand (CD40LG) and CD40 and the downregulated DEGs, such as striatin (STRN), were enriched in neuron projection development. In addition, nitric oxide synthase 1 (NOS1), a target of miRNA-125b, and myosin heavy chain 11 (MYH11), a target of minichromosome maintenance complex component 4 (MCM4), had higher degree scores in the integrated network. These findings suggest that CD40, CD40LG, NOS1, STRN, MCM4, MYH11 and miR-125b may be potential therapeutic targets for the treatment of IA.

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“…Intracranial aneurysm (IA), also known as cerebral aneurysm, is caused by the increase of intracranial pressure induced by the local abnormal widening of the cerebral artery cavity or arterial wall [1]. IA is a severe disease with high mortality and morbidity, and the prevalence rate is about 1-3% in the general population [2].…”

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“…Intracranial aneurysm (IA) is a kind of cerebrovascular disorder, which is featured by unconventionally bulged artery in the brain as well as subarachnoid hemorrhage (SAH) caused by IA rupture, accompanied with a high fatality and morbidity [1]. As is a destructive disease, the pathogenesis of IA has not been clarified [2]. IA is a rare familial form, but it is generally thought to be the result of acquired vascular injury caused by hypertension, smoking, and other traditional risk factors [3].…”

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“…The enrichment analysis results showed that the 31 DEGs were mainly enriched in biological processes that related to immunity, such as “immune system process” and “immune response.” It has been reported in many tumor diseases where the tumor development was intimately correlated with the immune system process and the immune response 15, 16, 17. It has also been reported that there is an association between immunity and IA disease 18, 19. These results showed that there is a close relationship between the DEGs and the development of IA.…”