Expression Profiling of Long Noncoding RNA and Messenger RNA in a Cecal Ligation and Puncture-Induced Colon Injury Mouse Model

Background: Emerging evidence reveals that long noncoding RNAs (lncRNAs) play important roles in the pathogenesis of sepsis. However, the detailed regulatory mechanisms of lncRNAs or whether certain lncRNA could serve as a biomarker in the septic colon remains unclear. The aim of this study was to investigate the profiles of lncRNAs and mRNAs in the septic colon through whole-transcriptome RNA Sequencing and to reveal the associated regulatory mechanism.

Method and result: We established a mouse model of sepsis by cecal ligation and puncture (CLP). Colon samples were collected upon CLP or sham surgery after 24 h. Whole-transcriptome RNA Sequencing was performed to profile the relative expressions of lncRNAs and mRNAs. 808 lncRNAs and 1509 mRNAs were differentially found in the septic group compared with the sham group. Bioinformatics analysis including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis (KEGG) was performed to predict the potential functions of these RNAs. GO analysis showed that the altered lncRNAs were enriched and involved in multiple immune responses, which may be a response to sepsis stress. KEGG analysis indicated that upregulated lncRNAs were significantly enriched in the p53 signaling pathway, NF-κB signaling pathway, and HIF-1 signaling pathway. Downregulated lncRNAs were mostly found to be involved in tight junction, leukocyte transendothelial migration, and HIF-1 signaling pathway.

Conclusion: Our results indicate that these altered lncRNAs and mRNAs may have crucial roles in the pathogenesis of sepsis. This study could contribute to extending the understanding of the function of lncRNAs in sepsis, which may help in searching for new diagnostic biomarkers and therapeutic targets to treat sepsis.