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外泌体 hsa_circRNA_104484 和 hsa_circRNA_104670 可能作为脓毒症潜在的新型生物标志物和治疗靶点。

Exosomal hsa_circRNA_104484 and hsa_circRNA_104670 may serve as potential novel biomarkers and therapeutic targets for sepsis.

机构信息

Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China.

出版信息

Sci Rep. 2021 Jul 8;11(1):14141. doi: 10.1038/s41598-021-93246-0.

Abstract

In order to explore the role of exosomal circRNAs in the occurrence and development of sepsis, we looked for potential diagnostic markers to accurately identify sepsis and to lay a molecular basis for precise treatment. Ultracentrifugation was used to extract exosomes from the serum of patients with sepsis and healthy individuals. Then, changes in circRNA expression in exosomes were studied by circRNA microarray analysis. Gene ontology (GO) analysis and Kyoto City Encyclopaedia of Genes and Genomes (KEGG) pathway analysis were used to annotate the biological functions and pathways of genes, and a circRNA-miRNA-mRNA regulatory network was constructed. In the microarray analysis, 132 circRNAs were significantly differentially expressed, including 80 and 52 that were upregulated and downregulated, respectively. RT-qPCR verified the results of microarray analysis: hsa_circRNA_104484 and hsa_circRNA_104670 were upregulated in sepsis serum exosomes. ROC analysis showed that hsa_circRNA_104484 and hsa_circRNA_104670 in serum exosomes have the potential to be used as diagnostic markers for sepsis. The circRNA-miRNA-mRNA network predicted the potential regulatory pathways of differentially expressed circRNAs. There are differences in the expression of circRNA in serum exosomes between patients with sepsis and healthy individuals, which may be involved in the occurrence and development of the disease. Among them, elevations in hsa_circRNA_104484 and hsa_circRNA_104670 could be used as novel diagnostic biomarkers and molecular therapeutic targets.

摘要

为了探讨外泌体 circRNAs 在脓毒症发生发展中的作用,我们寻找潜在的诊断标志物来准确识别脓毒症,并为精确治疗奠定分子基础。我们使用超速离心法从脓毒症患者和健康个体的血清中提取外泌体。然后,通过 circRNA 微阵列分析研究外泌体中 circRNA 表达的变化。基因本体 (GO) 分析和京都基因与基因组百科全书 (KEGG) 通路分析用于注释基因的生物学功能和通路,并构建 circRNA-miRNA-mRNA 调控网络。在微阵列分析中,有 132 个 circRNA 显著差异表达,其中 80 个上调,52 个下调。RT-qPCR 验证了微阵列分析的结果:hsa_circRNA_104484 和 hsa_circRNA_104670 在脓毒症血清外泌体中上调。ROC 分析表明,血清外泌体中的 hsa_circRNA_104484 和 hsa_circRNA_104670 具有作为脓毒症诊断标志物的潜力。circRNA-miRNA-mRNA 网络预测了差异表达 circRNA 的潜在调控途径。脓毒症患者和健康个体血清外泌体中 circRNA 的表达存在差异,这可能与疾病的发生发展有关。其中,hsa_circRNA_104484 和 hsa_circRNA_104670 的升高可作为新的诊断生物标志物和分子治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11a2/8266806/4cf562c68370/41598_2021_93246_Fig1_HTML.jpg

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