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生物信息学分析构建了参与颅内动脉瘤形成的潜在铁死亡相关ceRNA网络。

Bioinformatics analysis constructs potential ferroptosis-related ceRNA network involved in the formation of intracranial aneurysm.

作者信息

Zhu Huaxin, Tan Jiacong, Wang Zhihua, Wu Zhiwu, Zhou Wu, Zhang Zhixiong, Li Meihua, Zhao Yeyu

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

出版信息

Front Cell Neurosci. 2022 Oct 13;16:1016682. doi: 10.3389/fncel.2022.1016682. eCollection 2022.

Abstract

BACKGROUND

Intracranial aneurysm (IA) causes more than 80% of nontraumatic subarachnoid hemorrhages (SAHs). The mechanism of ferroptosis involved in IA formation remains unclear. The roles played by competitive endogenous RNA (ceRNA) regulation networks in many diseases are becoming clearer. The goal of this study was to understand more fully the ferroptosis-related ceRNA regulation network in IA.

MATERIALS AND METHODS

To identify differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and differentially expressed lncRNAs (DELs) across IA and control samples, the GEO datasets GSE122897 and GSE66239 were downloaded and analyzed with the aid of R. Ferroptosis DEGs were discovered by exploring the DEGs of ferroptosis-related genes of the ferroptosis database. Potentially interacting miRNAs and lncRNAs were predicted using miRWalk and StarBase. Enrichment analysis was also performed. We utilized the STRING database and Cytoscape software to identify protein-protein interactions and networks. DAB-enhanced Prussian blue staining was used to detect iron in IA tissues.

RESULTS

Iron deposition was evident in IA tissue. In all, 30 ferroptosis DEGs, 5 key DEMs, and 17 key DELs were screened out for constructing a triple regulatory network. According to expression regulation of DELs, DEMs, and DEGs, a hub triple regulatory network was built. As the functions of lncRNAs are determined by their cellular location, PVT1-hsa-miR-4644-SLC39A14 ceRNA and DUXAP8-hsa-miR-378e/378f-SLC2A3 ceRNA networks were constructed.

CONCLUSION

CeRNA (PVT1-hsa-miR-4644-SLC39A14 and DUXAP8-hsa-miR-378e/378f-SLC2A3) overexpression networks associated with ferroptosis in IA were established.

摘要

背景

颅内动脉瘤(IA)导致超过80%的非创伤性蛛网膜下腔出血(SAH)。铁死亡参与IA形成的机制尚不清楚。竞争性内源RNA(ceRNA)调控网络在许多疾病中所起的作用正变得越来越清晰。本研究的目的是更全面地了解IA中与铁死亡相关的ceRNA调控网络。

材料与方法

为了鉴定IA样本和对照样本中差异表达基因(DEG)、差异表达微小RNA(DEM)和差异表达长链非编码RNA(DEL),下载了GEO数据集GSE122897和GSE66239,并借助R进行分析。通过探索铁死亡数据库中铁死亡相关基因的DEG来发现铁死亡DEG。使用miRWalk和StarBase预测潜在相互作用的miRNA和lncRNA。还进行了富集分析。我们利用STRING数据库和Cytoscape软件来鉴定蛋白质-蛋白质相互作用和网络。采用DAB增强普鲁士蓝染色检测IA组织中的铁。

结果

IA组织中铁沉积明显。总共筛选出30个铁死亡DEG、5个关键DEM和17个关键DEL用于构建三重调控网络。根据DEL、DEM和DEG的表达调控,构建了一个枢纽三重调控网络。由于lncRNA的功能由其细胞定位决定,构建了PVT1-hsa-miR-4644-SLC39A14 ceRNA和DUXAP8-hsa-miR-378e/378f-SLC2A3 ceRNA网络。

结论

建立了与IA中铁死亡相关的ceRNA(PVT1-hsa-miR-4644-SLC39A14和DUXAP8-hsa-miR-378e/378f-SLC2A3)过表达网络。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb19/9612944/58dcee035dd0/fncel-16-1016682-g001.jpg

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