MicroRNA and their target mRNAs change expression in whole blood of patients after intracerebral hemorrhage
MicroRNA and their target mRNAs change expression in whole blood of patients after intracerebral hemorrhage
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DOI：
10.1177/0271678x19839501
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发表时间：
2020-04-01
影响因子：
6.3
通讯作者：
Stamova, Boryana
中科院分区：
文献类型：
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作者：
Cheng, Xiyuan;Ander, Bradley P.;Stamova, Boryana
先前的研究表明，大鼠和人类全血中的 mRNA 水平发生变化，以及脑出血 (ICH) 后大鼠全血中 miRNA 的变化。因此，本研究评估了 ICH 后人类全血中的 miRNA 及其假定的 mRNA 靶标。与匹配对照相比，全转录组分析发现 ICH 患者的 miRNA 和 mRNA 水平发生了变化。鉴定差异表达miRNA的靶标mRNA，并对miRNA-mRNA靶标进行功能分析。与对照相比，ICH 后 29 个 miRNA（22 个下调，7 个上调）和 250 个靶标 mRNA（136 个上调，114 个下调）和 7 个小核仁 RNA 表达发生变化（FDR < 0.05，倍数变化 >= |1.2|）。这些包括 Let7i、miR-146a-5p、miR210-5p、miR-93-5p、miR-221、miR-874、miR-17-3p、miR-378a-5p、miR-532-5p、mir-4707、miR-4450、mir-1183、Let-7d-3p、 miR-3937、miR-4288、miR-4741、 miR-92a-1-3p、miR-4514、mir-4658、mir-3689d-1、miR-4760-3p 和 mir-3183。通路分析显示受调节的 miRNA/mRNA 与 Toll 样受体、自然杀伤细胞、粘着斑、TGF-β、吞噬体、JAK-STAT、细胞因子细胞因子受体、趋化因子、细胞凋亡、血管平滑肌和 RNA 降解信号相关。其中许多途径与 ICH 有关。差异表达的 miRNA 及其推定的 mRNA 靶点和相关途径可能提供诊断生物标志物，并为人类 ICH 治疗指明治疗靶点。
Previous studies showed changes in mRNA levels in whole blood of rats and humans, and in miRNA in whole blood of rats following intracerebral hemorrhage (ICH). Thus, this study assessed miRNA and their putative mRNA targets in whole blood of humans following ICH. Whole transcriptome profiling identified altered miRNA and mRNA levels in ICH patients compared to matched controls. Target mRNAs of the differentially expressed miRNAs were identified, and functional analysis of the miRNA-mRNA targets was performed. Twenty-nine miRNAs (22 down, 7 up) and 250 target mRNAs (136 up, 114 down), and 7 small nucleolar RNA changed expression after ICH compared to controls (FDR < 0.05, and fold change >= |1.2|). These included Let7i, miR-146a-5p, miR210-5p, miR-93-5p, miR-221, miR-874, miR-17-3p, miR-378a-5p, miR-532-5p, mir-4707, miR-4450, mir-1183, Let-7d-3p, miR-3937, miR-4288, miR-4741, miR-92a-1-3p, miR-4514, mir-4658, mir-3689d-1, miR-4760-3p, and mir-3183. Pathway analysis showed regulated miRNAs/mRNAs were associated with toll-like receptor, natural killer cell, focal adhesion, TGF-beta, phagosome, JAK-STAT, cytokine-cytokine receptor, chemokine, apoptosis, vascular smooth muscle, and RNA degradation signaling. Many of these pathways have been implicated in ICH. The differentially expressed miRNA and their putative mRNA targets and associated pathways may provide diagnostic biomarkers as well as point to therapeutic targets for ICH treatments in humans.