Characterization of Dysregulated miRNA in Peripheral Blood Mononuclear Cells from Ischemic Stroke Patients.
Characterization of Dysregulated miRNA in Peripheral Blood Mononuclear Cells from Ischemic Stroke Patients.
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DOI：
10.1007/s12035-016-0347-8
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发表时间：
2018-03
影响因子：
5.1
通讯作者：
Nagarkatti M
中科院分区：
文献类型：
--
作者：
Bam M;Yang X;Sen S;Zumbrun EE;Dennis L;Zhang J;Nagarkatti PS;Nagarkatti M
表观遗传修饰可能在缺血性卒中（IS）风险的病理生理学中发挥重要作用。微小RNA（micro-RNAs，miRNAs）是表观遗传调控的一种模式，与包括IS在内的多种临床疾病有关。本研究的目的是研究IS患者外周血单个核细胞（PBMC）中的miRNA谱，并与无卒中对照组进行比较。从19名健康的年龄-性别-种族匹配的个体中获得血液样本，作为20名IS患者的对照。用来自PBMC的RNA进行miRNA微阵列分析，并鉴定了IS患者中常见的显著失调的miRNA。我们鉴定了117个线性倍数值至少为±1.5的miRNA，其中29个显著改变（p值< 0.05）。免疫途径分析（IPA）表明失调的miRNA在与IS相关的病症中的作用（例如，器官损伤和异常、血液学疾病和免疫学疾病）。促炎基因如STAT 3、白细胞介素（IL）12 A和IL 12 B是失调的miRNA的一些高度预测的靶点。值得注意的是，我们在所有IS患者中进一步鉴定了三种常见且显著上调的miRNA（hsa-miR-4656，−432，−503）和一种下调的miRNA（hsa-miR-874）。分子交互网络分析显示，通常失调的miRNAs共享几个与IS相关的作用靶点。总之，我们报告了IS PBMC中miRNA的失调，并为IS病理生理过程中它们参与免疫系统改变提供了证据。
Epigenetic modification may play an important role in pathophysiology of ischemic stroke (IS) risk. Micro-RNAs (miRNAs), which constitute one of the modes of epigenetic regulation, have been shown to be associated with a number of clinical disorders including IS. The purpose of this study was to investigate the miRNA profile in the peripheral blood mononuclear cells (PBMCs) of IS patients and compare it with stroke-free controls. Blood samples were obtained from 19 healthy age-gender-race matched individuals who served as controls to 20 IS patients. miRNA microarray analysis with RNA from PBMCs was performed and significantly dysregulated miRNAs common among IS patients were identified. We identified 117 miRNAs with linear fold values of at least ±1.5, of which, 29 were significantly altered (p value < 0.05). Ingenuity Pathway Analysis (IPA) indicated a role for the dysregulated miRNAs in conditions relevant to IS (e.g., organismal injury and abnormalities, hematological disease and immunological disease). Pro-inflammatory genes like STAT3, interleukin (IL) 12A and IL12B were some of the highly predicted targets for the dysregulated miRNAs. Notably, we further identified three common and significantly up-regulated miRNAs (hsa-miR-4656, −432, −503) and one downregulated miRNA (hsa-miR-874) amongst all IS patients. Molecular interactive network analysis revealed that the commonly dysregulated miRNAs share several targets with roles relevant to IS. Altogether, we report dysregulation of miRNAs in IS PBMCs and provide evidence for their involvement in the immune system alteration during IS pathophysiology.
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影响因子：
8.3
作者：
Lee, Soon-Tae;Chu, Kon;Roh, Jae-Kyu
通讯作者：
Roh, Jae-Kyu
影响因子：
4.1
作者：
Kawabori M;Yenari MA
通讯作者：
Yenari MA
影响因子：
4.2
作者：
Li M;Wang Y;Song Y;Bu R;Yin B;Fei X;Guo Q;Wu B
通讯作者：
Wu B
DOI：
10.1097/nen.0000000000000068
发表时间：
2014-05
影响因子：
3.2
作者：
Gesuete R;Kohama SG;Stenzel-Poore MP
通讯作者：
Stenzel-Poore MP
DOI：
10.4161/jkst.25097
发表时间：
2013-10-01
期刊：
JAK-STAT
影响因子：
--
作者：
Hutchins AP;Diez D;Miranda-Saavedra D
通讯作者：
Miranda-Saavedra D