Department of Infection, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Department of Neurosurgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3473-3480. doi: 10.3892/mmr.2017.8367. Epub 2017 Dec 29.
Intracranial aneurysm (IA) is a severe clinical condition of primary concern and currently, there is no effective therapeutic reagent. The present study aimed to investigate the molecular mechanism of IA via bioinformatic analysis. Various gene expression profiles (GSE26969) were downloaded from the Gene Expression Omnibus database, including 3 IA and 3 normal superficial temporal artery samples. Firstly, the limma package in R language was used to identify differentially expressed genes (DEGs; P‑value <0.01 and |log2 FC|≥1). Secondly, the database for annotation, visualization and integrated discovery software was utilized to perform pathway and functional enrichment analyses (false discovery rate ≤0.05). Finally, protein‑protein interaction (PPI) network and sub‑network clustering analyses were performed using the biomolecular interaction network database and ClusterONE software, respectively. Following this, a transcription factor regulatory network was identified from the PPI network. A total of 1,124 DEGs were identified, of which 989 were upregulated and 135 downregulated. Pathway and functional enrichment analyses revealed that the DEGs primarily participated in RNA splicing, functioning of the spliceosome, RNA processing and the mRNA metabolic process. Following PPI network analysis, 1 hepatocyte nuclear factor (HNF) 4A (transcription factor)‑centered regulatory network and 5 DEG‑centered sub‑networks were identified. On analysis of the transcription factor regulatory network, 6 transcription factors (HNF6, HNF4A, E2F4, YY1, H4 and H31T) and a regulatory pathway (HNF6‑HNF4‑E2F4) were identified. The results of the present study suggest that activating transcription factor‑5, Jun proto‑oncogene, activator protein‑1 transcription factor subunit, HNF6, HNF4 and E2F4 may participate in IA progression via vascular smooth muscle cell apoptosis, inflammation, vessel wall remodeling and damage and the tumor necrosis factor‑β signaling pathway. However, further experimental studies are required to validate these predictions.
颅内动脉瘤(IA)是一种严重的临床病症,目前尚无有效的治疗试剂。本研究旨在通过生物信息学分析探讨 IA 的分子机制。从基因表达综合数据库中下载了 3 个 IA 和 3 个正常颞浅动脉的基因表达谱(GSE26969),利用 R 语言中的 limma 包识别差异表达基因(DEGs;P 值<0.01,|log2 FC|≥1)。然后使用数据库进行注释、可视化和综合发现软件进行通路和功能富集分析(错误发现率≤0.05)。最后,利用生物分子相互作用网络数据库和 ClusterONE 软件分别进行蛋白质-蛋白质相互作用(PPI)网络和子网络聚类分析,然后从 PPI 网络中识别转录因子调控网络。共鉴定出 1124 个 DEGs,其中 989 个上调,135 个下调。通路和功能富集分析表明,DEGs 主要参与 RNA 剪接、剪接体功能、RNA 加工和 mRNA 代谢过程。通过 PPI 网络分析,鉴定出以肝细胞核因子(HNF)4A(转录因子)为中心的调控网络和 5 个以 DEG 为中心的子网络。在转录因子调控网络分析中,鉴定出 6 个转录因子(HNF6、HNF4A、E2F4、YY1、H4 和 H31T)和一个调控途径(HNF6-HNF4A-E2F4)。本研究结果表明,激活转录因子 5、Jun 原癌基因、激活蛋白 1 转录因子亚基、HNF6、HNF4 和 E2F4 可能通过血管平滑肌细胞凋亡、炎症、血管壁重塑和损伤以及肿瘤坏死因子-β信号通路参与 IA 的进展。然而,需要进一步的实验研究来验证这些预测。