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.

中文翻译：

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盲肠结扎和穿刺诱导的结肠损伤小鼠模型中长链非编码 RNA 和信使 RNA 的表达谱

背景。新出现的证据表明，长链非编码 RNA (lncRNA) 在脓毒症的发病机制中起重要作用。然而，lncRNA 的详细调控机制或某些 lncRNA 是否可以作为脓毒性结肠中的生物标志物仍不清楚。本研究的目的是通过全转录组 RNA 测序研究脓毒症结肠中 lncRNA 和 mRNA 的谱，并揭示相关的调控机制。方法和结果. 我们通过盲肠结扎和穿刺（CLP）建立了脓毒症小鼠模型。24 小时后在 CLP 或假手术后收集结肠样本。进行全转录组 RNA 测序以分析 lncRNA 和 mRNA 的相对表达。与假手术组相比，脓毒症组有 808 个 lncRNAs 和 1509 个 mRNAs 存在差异。进行生物信息学分析，包括基因本体论 (GO) 分析和京都基因百科全书和基因组通路分析 (KEGG)，以预测这些 RNA 的潜在功能。GO分析表明，改变的lncRNAs富集并参与多种免疫反应，这可能是对脓毒症应激的反应。KEGG 分析表明，上调的 lncRNA 在 p53 信号通路、NF- κ中显着富集。B信号通路和HIF-1信号通路。下调的 lncRNA 主要参与紧密连接、白细胞跨内皮迁移和 HIF-1 信号通路。结论。我们的研究结果表明，这些改变的 lncRNA 和 mRNA 可能在脓毒症的发病机制中起关键作用。这项研究可能有助于扩展对 lncRNA 在脓毒症中功能的理解，这可能有助于寻找新的诊断生物标志物和治疗靶点来治疗脓毒症。