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整合mRNA和miRNA表达谱探索缺血性脑卒中的分子机制

Molecular Mechanism Exploration of Ischemic Stroke by Integrating mRNA and miRNA Expression Profiles.

作者信息

Bao Jianhong, Zhou Saijun, Pan Sipei, Zhang Yang

出版信息

Clin Lab. 2018 Apr 1;64(4):559-568. doi: 10.7754/Clin.Lab.2017.171044.

DOI:10.7754/Clin.Lab.2017.171044
PMID:29739082
Abstract

BACKGROUND

Stroke is one of the leading causes of death worldwide, and ischemic stroke accounts for about 80 percent of all cases. Ischemic stroke is usually caused by a blockage in an artery to the brain. However, its molecular mechanisms remain largely unclear. The integration of mRNA and miRNA expression patterns is an effective strategy to investigate the potential molecular mechanisms of ischemic stroke in posttranscriptional regulation level.

METHODS

The mRNA and miRNA expression data were downloaded from the GEO database. The genes and miRNAs with fold change ≥ 1.5 and p-value ≤ 0.05 were considered differential expressions. GO and KEGG pathway annotations of differentially expressed genes were performed to investigate the potential biology function. The constructed mRNA-miRNA interaction networks were used to identify new genes and molecular mechanism of ischemic stroke.

RESULTS

Three hundred thirty-eight DEGs (differentially expressed genes) in mRNA expression data were collected from blood samples of 23 patients with ischemic stroke and 23 vascular risk factor controls, and 8 miRNAs from peripheral blood cells of 48 patients with ischemic stroke and vascular risk factor controls. By analyzing the mRNA-miRNA regulation network, 6 miRNAs are responsible for the differential expression of 63 DEGs. Among these miRNAs, 4 screened miRNAs were shown to regulate oxidative stress, apoptosis, and thrombus formation of ischemic stroke in previous reports. In addition, the predicted target genes, such as BCL2A1 and TPM2, showed a crucial or potential role in the pathogenic mechanism of ischemic stroke.

CONCLUSIONS

These results deciphered posttranscriptional regulation of the molecular mechanism of ischemic stroke and identified valuable genes in the development process of ischemic stroke.

摘要

背景

中风是全球主要的死亡原因之一,缺血性中风约占所有病例的80%。缺血性中风通常由大脑动脉堵塞引起。然而,其分子机制仍 largely不清楚。整合mRNA和miRNA表达模式是在转录后调控水平研究缺血性中风潜在分子机制的有效策略。

方法

从GEO数据库下载mRNA和miRNA表达数据。将折叠变化≥1.5且p值≤0.05的基因和miRNA视为差异表达。对差异表达基因进行GO和KEGG通路注释以研究潜在的生物学功能。构建的mRNA-miRNA相互作用网络用于识别缺血性中风的新基因和分子机制。

结果

从23例缺血性中风患者和23例血管危险因素对照的血液样本中收集了mRNA表达数据中的338个差异表达基因(DEGs),以及48例缺血性中风患者和血管危险因素对照的外周血细胞中的8个miRNA。通过分析mRNA-miRNA调控网络,6个miRNA负责63个DEGs的差异表达。在这些miRNA中,4个筛选出的miRNA在先前的报告中显示可调节缺血性中风的氧化应激、细胞凋亡和血栓形成。此外,预测的靶基因,如BCL2A1和TPM2,在缺血性中风的致病机制中显示出关键或潜在作用。

结论

这些结果解读了缺血性中风分子机制的转录后调控,并在缺血性中风的发展过程中鉴定出有价值的基因。

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