Screening Of MiRNAs That Augment Sepsis AKI Using Bioinformatics

BACKGROUND:Sepsis combined with acute renal failure increases the risk of death in patients.To understand the pathogenesis of sepsis and acute kidney injury,and to increase clinical intervention can reduce acute kidney injury in patients with sepsis,thereby reducing mortality in critically ill patients.MicroRNAs(miRNAs)can fine-tune gene expression and protein synthesis and participate in the occurrence and progression of disease.There is evidence that miRNAs are expected to be potential diagnostic and therapeutic tools for early identification of AKI.OBJECTIVE:To analyze the gene expression profile GSE67401 in the GEO database by using bioinformatics methods,attempts were made to screen for miRNAs involved in the regulation of AKI in sepsis and to promote the potential pathway of AKI.METHODS:The GSE67401 raw data set was downloaded from the GEO database.The samples were divided into systemic inflammatory response syndrome(SIRS)with acute kidney injury group(n=58)and normal renal function with SIRS according to the annotation file in the GSE67401 data set.Group(n=53),obtained a sample miRNA expression matrix.Differentially expressed miRNAs were identified using the R software limma(p<0.05,fold change>2)and potential target genes were predicted using the miRTarBase database.Functional annotation and pathway enrichment analysis of these potential targets of DE-miRNA were performed using the Enricher database.A protein-protein interaction network was constructed from the STRING database and visualized by Cytoscape software to screen out pivot genes and construct potential target genes and miRNA-gene regulatory networks.RESULTS:In SIRS patients,a total of 101 DE-miRNAs were screened for acute kidney injury compared with no acute kidney injury,including 15 up-regulated miRNAs and 86 down-regulated miRNAs,of which hsa-miR-4330,hsa-miR-217,hsa-miR-4671-3p,hsa-miR-2681-3p,hsa-miR-93-3p are the top 5 most up-regulated,hsa-miR-4536-3p,hsa-miR-525-3p,hsa-miR-3975,hsa-miR-188-3p,hsa-miR-3684 are the top 5 most downregulated.312 potential target genes of the five most up-regulated miRNAs and 259 potential target genes of the five most down-regulated miRNAs were predicted,respectively,wherein the target genes of the up-regulated miRNAs were enriched in oxidative stress-related pathways,such as HIF-1 signaling Pathway,p53 signaling pathway,PI3K-Akt signaling pathway,FOXO signaling pathway,mTOR signaling pathway,etc.In a PPI network,the top 20 central nodes with a higher number of nodes are identified as hub genes.Most of the pivotal genes corresponding to up-regulated miRNAs are involved in the oxidative stress process.Conclusion:Different expression of miRNA may potentially be used to distinguish between sepsis AKI and sepsis non-AKI,and they are involved in the regulation of mitochondrial oxidative stress and dysfunction,including regulatory genes STRT1,PTEN,FOXO3 and so on.Among them,has-miR-217 may be involved in oxidative stress.Targeting has-miR-217 may provide an effective and promising approach for the identification and treatment of sepsis AKI.