School of Life and Pharmaceutical Sciences, Dalian University of Technology, Dalian, China.
Department of Cardiovascular Surgery, The General Hospital of the PLA Rocket Force, Beijing Normal University, Beijing, China.
Dis Markers. 2021 Nov 5;2021:9916881. doi: 10.1155/2021/9916881. eCollection 2021.
BACKGROUND: Abdominal aortic aneurysm (AAA) is a progressive cardiovascular disease, which is a permanent and localized dilatation of the abdominal aorta with potentially fatal consequence of aortic rupture. Dysregulation of circRNAs is correlated with the development of various pathological events in cardiovascular diseases. However, the function of circRNAs in abdominal aortic aneurysm (AAA) is unknown and remains to be explored. This study is aimed at determining the regulatory mechanisms of circRNAs in AAAs. This study was aimed at exploring the underlying molecular mechanisms of abdominal aortic aneurysms based on the competing endogenous RNA (ceRNA) regulatory hypothesis of circRNA, miRNA, and mRNA. METHODS: The expression profiles of circRNAs (GSE144431), miRNAs (GSE62179), and mRNAs (GSE7084, GSE57691, and GSE47472) in human tissue sample from the aneurysm group and normal group were obtained from the Gene Expression Omnibus database, respectively. The circRNA-miRNA-mRNA network was constructed by using Cytoscape 3.7.2 software; then, the protein-protein interaction (PPI) network was constructed by using the STRING database, and the hub genes were identified by using the cytoHubba plug-in. The circRNA-miRNA-hub gene regulatory subnetwork was formed to understand the regulatory axis of hub genes in AAAs. RESULTS: The present study identified 40 differentially expressed circRNAs (DECs) in the GSE144431, 90 differentially expressed miRNAs (DEmiRs) in the GSE62179, and 168 differentially expressed mRNAs (DEGs) with the same direction regulation (130 downregulated and 38 upregulated) in the GSE7084, GSE57691, and GSE47472 datasets identified regarding AAAs. The miRNA response elements (MREs) of three DECs were then predicted. Four overlapping miRNAs were obtained by intersecting the predicted miRNA and DEmiRs. Then, 17 overlapping mRNAs were obtained by intersecting the predicted target mRNAs of 4 miRNAs with 168 DEGs. Furthermore, the circRNA-miRNA-mRNA network was constructed through 3 circRNAs, 4 miRNAs, and 17 mRNAs, and three hub genes (SOD2, CCR7, and PGRMC1) were identified. Simultaneously, functional enrichment and pathway analysis were performed within genes in the circRNA-miRNA-mRNA network. Three of them (SOD2, CCR7, and PGRMC1) were suggested to be crucial based on functional enrichment, protein-protein interaction, and ceRNA network analysis. Furthermore, the expression of SOD2 and CCR7 may be regulated by hsa_circ_0011449/hsa_circ_0081968/hsa-let-7f-5p; the expression of PGRMC1 may be regulated by hsa_circ_0011449/hsa_circ_0081968-hsa-let-7f-5p/hsa-let-7e-5p. CONCLUSION: In conclusion, the ceRNA interaction axis we identified may be an important target for the treatment of abdominal aortic aneurysms. This study provided further understanding of the potential pathogenesis from the perspective of the circRNA-related competitive endogenous RNA network in AAAs.
背景:腹主动脉瘤(AAA)是一种进行性心血管疾病,是腹主动脉的永久性和局部扩张,可能导致主动脉破裂的致命后果。环状 RNA 的失调与心血管疾病中各种病理事件的发展有关。然而,circRNA 在腹主动脉瘤(AAA)中的功能尚不清楚,有待进一步研究。本研究旨在确定 circRNAs 在 AAAs 中的调控机制。本研究旨在基于环状 RNA、miRNA 和 mRNA 的竞争内源性 RNA(ceRNA)调控假说,探讨基于组织学标本的腹主动脉瘤的潜在分子机制。
方法:从基因表达综合数据库中分别获得人组织样本中来自动脉瘤组和正常组的 circRNAs(GSE144431)、miRNAs(GSE62179)和 mRNAs(GSE7084、GSE57691 和 GSE47472)的表达谱。使用 Cytoscape 3.7.2 软件构建 circRNA-miRNA-mRNA 网络;然后,使用 STRING 数据库构建蛋白质-蛋白质相互作用(PPI)网络,并使用 cytoHubba 插件识别枢纽基因。形成 circRNA-miRNA-枢纽基因调控子网络,以了解 AAAs 中枢纽基因的调控轴。
结果:本研究在 GSE144431 中鉴定出 40 个差异表达的 circRNAs(DECs),在 GSE62179 中鉴定出 90 个差异表达的 miRNAs(DEmiRs),在 GSE7084、GSE57691 和 GSE47472 数据集鉴定出 168 个具有相同方向调节(130 个下调和 38 个上调)的差异表达 mRNAs(DEGs)。然后预测了三个 DECs 的 miRNA 反应元件(MREs)。通过 intersecting 预测的 miRNA 和 DEmiRs 获得四个重叠的 miRNAs。然后,通过 intersecting 四个 miRNA 预测的靶 mRNAs 与 168 个 DEGs 获得 17 个重叠的 mRNAs。此外,通过 3 个 circRNAs、4 个 miRNAs 和 17 个 mRNAs 构建了 circRNA-miRNA-mRNA 网络,并鉴定出三个枢纽基因(SOD2、CCR7 和 PGRMC1)。同时,在 circRNA-miRNA-mRNA 网络中的基因内进行了功能富集和通路分析。基于功能富集、蛋白质-蛋白质相互作用和 ceRNA 网络分析,其中三个(SOD2、CCR7 和 PGRMC1)被认为是关键的。此外,SOD2 和 CCR7 的表达可能受 hsa_circ_0011449/hsa_circ_0081968/hsa-let-7f-5p 的调节;PGRMC1 的表达可能受 hsa_circ_0011449/hsa_circ_0081968-hsa-let-7f-5p/hsa-let-7e-5p 的调节。
结论:总之,我们鉴定的 ceRNA 相互作用轴可能是治疗腹主动脉瘤的重要靶点。本研究从 AAAs 中环状 RNA 相关竞争性内源性 RNA 网络的角度进一步了解了潜在的发病机制。
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