Identification of lncRNAs in peripheral blood mononuclear cells associated with sepsis immunosuppression based on weighted gene co-expression network analysis.

IF 2.5 3区 生物学
Wenjia Zhang, Yan Li, Gang Li, Aijia Zhang, Wende Sun
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引用次数: 0

Abstract

Background: Sepsis-induced immunosuppression involves complex molecular mechanisms, including dysregulated long noncoding RNAs (lncRNAs), which remain poorly understood.

Objective: We aimed to identify immunosuppression-related lncRNAs and their functional pathways in sepsis. Methods: Using weighted gene coexpression network analysis (WGCNA), we analyzed lncRNA profiles from peripheral blood mononuclear cells (PBMCs) of three sepsis patients and three healthy controls. Key modules linked to immunosuppression were validated via RT-PCR and external datasets. Pathway enrichment and protein interaction networks were employed to prioritize mechanisms.

Results: A sepsis-associated module containing 4,193 lncRNAs revealed three immunosuppression-related pathways: Th17 cell differentiation, cytokine-cytokine receptor interactions, and cancer-related proteoglycan signaling. Protein-protein interaction networks identified three central genes (SLFN12, ICOS, IKZF2) and their linked lncRNAs (ENSG00000267074, lnc-ICOSLG-1, lnc-IKZF2-7), all significantly downregulated in sepsis patients.

Conclusion:  Our findings highlight novel lncRNA-regulated pathways in sepsis-induced immunosuppression, providing potential targets for improved diagnosis and therapy.

基于加权基因共表达网络分析的外周血单核细胞中与脓毒症免疫抑制相关的lncrna鉴定
背景:脓毒症诱导的免疫抑制涉及复杂的分子机制,包括长链非编码rna (lncRNAs)的失调,这一机制尚不清楚。目的:我们旨在鉴定免疫抑制相关的lncrna及其在败血症中的功能途径。方法:采用加权基因共表达网络分析(WGCNA)对3例败血症患者和3例健康对照者外周血单个核细胞(PBMCs)的lncRNA谱进行分析。通过RT-PCR和外部数据集验证与免疫抑制相关的关键模块。途径富集和蛋白质相互作用网络被用来确定机制的优先级。结果:一个包含4193个lncRNAs的脓毒症相关模块揭示了三条免疫抑制相关途径:Th17细胞分化、细胞因子-细胞因子受体相互作用和癌症相关的蛋白聚糖信号传导。蛋白-蛋白相互作用网络鉴定出三个中心基因(SLFN12、ICOS、IKZF2)及其相关lncrna (ENSG00000267074、lnc-ICOSLG-1、lnc-IKZF2-7)在脓毒症患者中均显著下调。结论:我们的研究结果突出了lncrna调控的脓毒症诱导免疫抑制的新途径,为改进诊断和治疗提供了潜在的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Hereditas
Hereditas Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.80
自引率
3.70%
发文量
0
期刊介绍: For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.
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