{"title":"Analysis of ceRNA Network and Identification of Potential Treatment Target and Biomarkers of Endothelial Cell Injury in Sepsis.","authors":"Yulin Li, Qinghui Fu, Junjun Fang, Zhipeng Xu, Chunhu Zhang, Longwei Tan, Xin Liao, Yao Wu","doi":"10.1089/gtmb.2023.0143","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Background:</i></b> 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. <b><i>Methods:</i></b> 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 <i>in vitro</i> model of sepsis for network verification. Reverse transcription-polymerase chain reaction, fluorescence <i>in situ</i> hybridization, and luciferase reporter genes were used to verify the bioinformatic analysis. <b><i>Result:</i></b> 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 <i>ZFAS1</i> 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 <i>SLC26A6</i> was an independent predictor of prognosis in sepsis. Overall, our findings indicated that the <i>ZFAS1</i>/hsa-miR-449c-5p/<i>SLC26A6</i> ceRNA regulatory axis may play a role in the progression of sepsis. <b><i>Conclusion:</i></b> The sepsis ceRNA network, especially the <i>ZFAS1</i>/hsa-miR-449c-5p/<i>SLC26A6</i> regulatory axis, is expected to reveal potential biomarkers and therapeutic targets for sepsis management.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"133-143"},"PeriodicalIF":1.1000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetic testing and molecular biomarkers","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/gtmb.2023.0143","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/19 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
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.
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