Cheng Yanwei, Cao Xue, Zhang Jiange, Chen Dong, Zhu Juan, Xu Lijun, Qin Lijie
Department of Emergency, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China.
Department of Rheumatology and Immunology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China.
Front Pharmacol. 2021 Aug 17;12:678256. doi: 10.3389/fphar.2021.678256. eCollection 2021.
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 manner. The lncRNA-mRNA network and the qRT-PCR test revealed that lncRNAs , , and were significantly correlated with the pathogenesis of sepsis. In addition, weighted gene co-expression analysis (WGCNA) and -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.
脓毒症是一种高度异质性的综合征,由宿主对感染的失衡反应引起。据报道,长链非编码RNA(lncRNAs)在多种生物学过程中发挥调节作用,并成为多种疾病的潜在生物标志物和治疗靶点。然而,目前对lncRNAs在脓毒症中作用的了解极为有限。在此,为了解析lncRNAs的潜在功能,我们重新探索了来自脓毒症标本、最终诊断为非脓毒症的标本以及对照的83个转录组数据集。获得了差异表达基因(DEGs)、差异表达lncRNA(DElncRNA)分析以及lncRNA-mRNA对的共表达分析结果。我们发现lncRNAs的表达模式在脓毒症标本中显著激活,在脓毒症中与非脓毒症和对照标本有明显区别。通过进行共表达分析,我们发现DElncRNAs通过以这种方式调节mRNA表达,与脓毒症中T细胞活化和免疫反应相关术语密切相关。lncRNA-mRNA网络和qRT-PCR测试表明lncRNAs 、 和 与脓毒症的发病机制显著相关。此外,加权基因共表达分析(WGCNA)和调控分析还表明,脓毒症特异性lncRNAs与脓毒症相关的重要生物学过程高度相关。总之,lncRNAs的系统性失调紧密参与脓毒症基因表达调控网络的重塑,lncRNA-mRNA表达网络可用于完善生物标志物预测,以开发脓毒症的新型治疗方法。