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.
Highlights
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
Our diagnosis of sepsis mainly relies on Sequential Organ Failure Assessment (SOFA) scoring system, which has certain limitations; currently, there is no ‘gold standard’ for laboratory diagnosis
The serum exosome was confirmed by transmission electron microscopy (TEM) and WB for CD63 or TSG101 (Fig. 1a)
Summary
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. 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. With the development of high-throughput sequencing technology, genomics and metabolomics analyses have found that the levels of various genes and metabolites in sepsis have changed, and that the changes occur earlier than clinical symptoms[3,4] Identifying these molecular changes in sepsis is highly valuable for understanding the course of the disease, and for predicting prognosis and response to treatment. Individualised therapy targeting the core molecules of the disease can improve the efficiency of the treatment and reduce toxicity These differentially expressed molecules may serve as diagnostic markers for sepsis and may become targets for molecular targeted therapy.
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