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缺血性卒中中免疫细胞相关基因特征及免疫调节性竞争性内源RNA的分析

Profiling immune cell-related gene features and immunoregulatory ceRNA in ischemic stroke.

作者信息

Li Yanbo, Liu Sicheng, Wen Linda, Zhang Linzhu, Lei Xue, Zhang Yaguang, Qiu Lei, He Li, Han Junhong

机构信息

Department of Gastrointestinal Surgery, Cancer Center and State Key Laboratory of Biotherapy, and Frontiers Science Center for Disease-Related Molecular Network, Laboratory of Gastrointestinal Tumor Epigenetics and Genomics, West China Hospital, Sichuan University, Chengdu, 610041, China.

Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, China.

出版信息

Mol Biomed. 2024 Dec 18;5(1):72. doi: 10.1186/s43556-024-00237-4.

Abstract

Molecules in immune cells plays a vital role in the pathogenesis of ischemic stroke (IS). The aim of this study is to profile the landscape of molecules on the basis of immune cells in IS peripheral blood and construct an immunoregulatory competing endogenous RNA (ceRNA) network. We collected and combined multiple public transcriptome datasets from the peripheral blood of IS patients and healthy controls. CIBERSORT deconvolution revealed that the proportions of CD8 and CD4 naive T cells, monocytes, and neutrophils changed significantly in the IS group. Intersecting the immune cell-related genes identified by weighted gene co-expression network analysis (WGCNA) and differential expression analysis, 38 overlapping candidate biomarkers were selected. Three machine learning algorithms, including least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest were applied, and 11 distinct immune cell-related genes were identified. We obtained the mRNA-miRNA and miRNA-lncRNA interactions from StarBase v3.0, and constructed a ceRNA network based on the differentially expressed mRNAs, miRNAs, and lncRNAs. The aberrant expression of HECW2-centered ceRNAs in the peripheral blood of in-house patients was validated using quantitative PCR. We also revealed that the expression of HECW2 was positively correlated with lncRNAs LINC02593 through miRNAs miR-130a-3p, miR-130b-3p and miR-148b-3p in cells. These results show that there are distinct immune features between IS patients and healthy controls. The ceRNA network may help elucidate the mechanism of immune cell-related genes in IS and may serve as a therapeutic target.

摘要

免疫细胞中的分子在缺血性中风(IS)的发病机制中起着至关重要的作用。本研究的目的是基于IS患者外周血中的免疫细胞来描绘分子图谱,并构建一个免疫调节竞争性内源性RNA(ceRNA)网络。我们收集并整合了来自IS患者和健康对照外周血的多个公共转录组数据集。CIBERSORT反卷积分析显示,IS组中CD8和CD4初始T细胞、单核细胞和中性粒细胞的比例发生了显著变化。通过加权基因共表达网络分析(WGCNA)和差异表达分析确定的免疫细胞相关基因进行交叉分析,选择了38个重叠的候选生物标志物。应用了三种机器学习算法,包括最小绝对收缩和选择算子(LASSO)、支持向量机递归特征消除(SVM-RFE)和随机森林,鉴定出11个不同的免疫细胞相关基因。我们从StarBase v3.0获得了mRNA-miRNA和miRNA-lncRNA相互作用,并基于差异表达的mRNA、miRNA和lncRNA构建了一个ceRNA网络。使用定量PCR验证了内部患者外周血中以HECW2为中心的ceRNAs的异常表达。我们还发现,在细胞中,HECW2的表达通过miRNA miR-130a-3p、miR-130b-3p和miR-148b-3p与lncRNAs LINC02593呈正相关。这些结果表明,IS患者和健康对照之间存在明显的免疫特征。ceRNA网络可能有助于阐明IS中免疫细胞相关基因的机制,并可能作为治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb9/11652561/d29b647ec150/43556_2024_237_Fig1_HTML.jpg

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