Analysis of ceRNA Network and Identification of Potential Treatment Target and Biomarkers of Endothelial Cell Injury in Sepsis.

IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Genetic testing and molecular biomarkers Pub Date : 2024-04-01 Epub Date: 2024-03-19 DOI:10.1089/gtmb.2023.0143
Yulin Li, Qinghui Fu, Junjun Fang, Zhipeng Xu, Chunhu Zhang, Longwei Tan, Xin Liao, Yao Wu
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Abstract

Background: Sepsis is a complex clinical syndrome caused by a dysregulated host immune response to infection. This study aimed to identify a competing endogenous RNA (ceRNA) network that can greatly contribute to understanding the pathophysiological process of sepsis and determining sepsis biomarkers. Methods: The GSE100159, GSE65682, GSE167363, and GSE94717 datasets were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene coexpression network analysis was performed to find modules possibly involved in sepsis. A long noncoding RNA-microRNA-messenger RNA (lncRNA-miRNA-mRNA) network was constructed based on the findings. Single-cell analysis was performed. Human umbilical vein endothelial cells were treated with lipopolysaccharide (LPS) to create an in vitro model of sepsis for network verification. Reverse transcription-polymerase chain reaction, fluorescence in situ hybridization, and luciferase reporter genes were used to verify the bioinformatic analysis. Result: By integrating data from three GEO datasets, we successfully constructed a ceRNA network containing 18 lncRNAs, 7 miRNAs, and 94 mRNAs based on the ceRNA hypothesis. The lncRNA ZFAS1 was found to be highly expressed in LPS-stimulated endothelial cells and may thus play a role in endothelial cell injury. Univariate and multivariate Cox analyses showed that only SLC26A6 was an independent predictor of prognosis in sepsis. Overall, our findings indicated that the ZFAS1/hsa-miR-449c-5p/SLC26A6 ceRNA regulatory axis may play a role in the progression of sepsis. Conclusion: The sepsis ceRNA network, especially the ZFAS1/hsa-miR-449c-5p/SLC26A6 regulatory axis, is expected to reveal potential biomarkers and therapeutic targets for sepsis management.

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分析 ceRNA 网络并确定潜在治疗目标和败血症内皮细胞损伤生物标志物
背景:败血症是一种复杂的临床综合征,由宿主对感染的免疫反应失调引起。本研究旨在确定一个竞争性内源性 RNA(ceRNA)网络,该网络可大大有助于理解败血症的病理生理过程并确定败血症生物标志物。研究方法GSE100159、GSE65682、GSE167363和GSE94717数据集来自基因表达总库(GEO)数据库。通过加权基因共表达网络分析,找到了可能与败血症有关的模块。根据分析结果构建了长非编码RNA-微RNA-信使RNA(lncRNA-miRNA-mRNA)网络。进行了单细胞分析。用脂多糖(LPS)处理人脐静脉内皮细胞,建立脓毒症体外模型,以验证网络。使用反转录聚合酶链反应、荧光原位杂交和荧光素酶报告基因验证生物信息分析。结果通过整合三个GEO数据集的数据,我们根据ceRNA假说成功构建了一个包含18个lncRNA、7个miRNA和94个mRNA的ceRNA网络。研究发现,lncRNA ZFAS1在LPS刺激的内皮细胞中高表达,因此可能在内皮细胞损伤中发挥作用。单变量和多变量Cox分析显示,只有SLC26A6是脓毒症预后的独立预测因子。总之,我们的研究结果表明,ZFAS1/hsa-miR-449c-5p/SLC26A6 ceRNA调控轴可能在脓毒症的进展中发挥作用。结论脓毒症 ceRNA 网络,尤其是 ZFAS1/hsa-miR-449c-5p/SLC26A6 调控轴,有望为脓毒症治疗揭示潜在的生物标记物和治疗靶点。
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来源期刊
CiteScore
2.50
自引率
7.10%
发文量
63
审稿时长
1 months
期刊介绍: Genetic Testing and Molecular Biomarkers is the leading peer-reviewed journal covering all aspects of human genetic testing including molecular biomarkers. The Journal provides a forum for the development of new technology; the application of testing to decision making in an increasingly varied set of clinical situations; ethical, legal, social, and economic aspects of genetic testing; and issues concerning effective genetic counseling. This is the definitive resource for researchers, clinicians, and scientists who develop, perform, and interpret genetic tests and their results. Genetic Testing and Molecular Biomarkers coverage includes: -Diagnosis across the life span- Risk assessment- Carrier detection in individuals, couples, and populations- Novel methods and new instrumentation for genetic testing- Results of molecular, biochemical, and cytogenetic testing- Genetic counseling
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