AUTHOR=Li Yang , Zhang Zhen , Liu Donghua 

TITLE=Intracranial Aneurysms Induced by RUNX1 Through Regulation of NFKB1 in Patients With Hypertension-An Integrated Analysis Based on Multiple Datasets and Algorithms

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.877801

DOI=10.3389/fneur.2022.877801

ISSN=1664-2295

ABSTRACT=<sec><title>Objective</title><p>The purpose of this study was to identify potential therapeutic targets by examining the hub genes contributing to progression of intracranial aneurysm (IA) in patients with hypertension.</p></sec><sec><title>Methods</title><p>The bulk RNA sequencing (RNA-seq) datasets of hypertension and IA were obtained from the Gene Expression Omnibus (<ext-link ext-link-type="uri" xlink:href="http://www.ncbi.nlm.nih.gov/geo" xmlns:xlink="http://www.w3.org/1999/xlink">www.ncbi.nlm.nih.gov/geo</ext-link>) database. These data were then used to calculate disease-related differentially expressed genes (DEGs) at the individual level. An scRNA-seq dataset of patients with abdominal aortic aneurysms (AAA) was used to analyze monocyte/macrophage-related DEGs. On the basis of the DEG data related to monocytes and macrophages, a TF-genes network has been developed. Hub genes and core sub-networks have also been identified. Furthermore, the key genes have been validated in an external cohort.</p></sec><sec><title>Results</title><p>From combined monocyte and macrophage-derived DEGs from abdominal aortic aneurysms, five hub DEGs were detected, including <italic>IFI30, SERPINE1, HMOX1, IL24</italic>, and <italic>RUNX1</italic>. A total of 57 genes were found in the IA bulk RNA-seq dataset. A support vector machine-recursive feature elimination algorithm (SVM-RFE) was applied to further screen the seven genes (<italic>RPS4Y1, DDX3Y, RUNX1, CLEC10A, PLAC8, SLA, and LILRB3</italic>). <italic>RUNX1</italic> was the hub gene that regulated <italic>NFKB1</italic> in the monocyte/macrophage-related network. And <italic>RUNX1</italic> is implicated in IA progression by regulating hematopoietic stem cell differentiation and abnormal platelet production, according to gene set enrichment analysis.</p></sec><sec><title>Conclusion</title><p>Among patients with hypertension, <italic>RUNX1</italic> in monocytes and macrophages was associated with a higher risk of IA through its regulation of <italic>NFKB1</italic>.</p></sec>