Abstract
Sepsis is a highly heterogeneous syndrome that is caused by an unbalanced host response to an infection. Long noncoding RNAs (lncRNAs) have been reported to exert regulatory roles in a variety of biological processes, and became potential biomarkers and therapeutic targets for diverse diseases. However, current understanding on the roles of lncRNAs in sepsis is extremely limited. Herein, to decipher the underlying functions of lncRNAs, we reexplored the 83 transcriptome datasets from specimens with sepsis, no_sepsis by final diagnosis, and control. The results of differentially expressed genes (DEGs), differentially expressed lncRNA (DElncRNA) analysis, and co-expression analysis of lncRNA–mRNA pairs were obtained. We found that the expression pattern of lncRNAs was significantly activated in sepsis specimens, which was clearly distinguished in sepsis from no_sepsis and control specimens. By performing co-expression analysis, we found DElncRNAs were closely related to T-cell activation and immune response–related terms in sepsis by regulating mRNA expression in the trans manner. The lncRNA–mRNA network and the qRT-PCR test revealed that lncRNAs LINC00861, RP11-284N8.3, and CTB-61M7.2 were significantly correlated with the pathogenesis of sepsis. In addition, weighted gene co-expression analysis (WGCNA) and cis-regulation analysis also revealed sepsis-specific lncRNAs were highly associated with important biological processes correlated with sepsis. In summary, the systematic dysregulation of lncRNAs is tightly involved in the remodeling of gene expression regulatory network in sepsis, and the lncRNA–mRNA expression network may be used to refine biomarker predictions for developing novel therapeutic approaches in sepsis.
Highlights
Sepsis is defined as a life-threatening multi-organ dysfunction caused by a dysregulated host response to infection (Singer et al, 2016)
By comparing the exon number of Long noncoding RNAs (lncRNAs) and mRNAs, we found more than 90% of novel lncRNAs only had one exon, which was distinct from known lncRNAs and mRNAs (Supplementary Figure 1B)
Besides exerting a role in the pathogenesis to fatty liver disease, obesity, atherosclerosis, diabetes, neurological disorders, and specific types of cancer (Yan et al, 2015), ACSL1 palys a likely role in driving inflammasomemediated release of pro-inflammatory factors by neutrophils during sepsis, based on both profiling of the literature (AlRashed et al, 2019; Kalugotla et al, 2019; Roelands et al, 2019) and transcript co-expression analysis (Cheng et al, 2016). These results indicated that the transacting DElncRNAs of the co-expression network involved in the pathogenesis of sepsis mainly through participating in T cell activation and immune response
Summary
Sepsis is defined as a life-threatening multi-organ dysfunction caused by a dysregulated host response to infection (Singer et al, 2016). It should be noted that patients who survive sepsis often suffer from a poor long-term outcome with risk of cognitive and physical impairments (Iwashyna et al, 2010). In light of this fact, sepsis has been described as the quintessential medical disorder of the twenty-first century (Reinhart et al, 2017). In such a context, substantial research progress has been made in recent years to understand the basic mechanisms underlying sepsis pathogenesis and to identify potential biomarkers and targets for use as diagnostic, therapeutic, and prognostic tools. Special attention has been paid to investigate the roles of long noncoding RNAs (lncRNAs) in sepsis
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