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miRNA 依赖性调控在血栓性疾病中 DNMT 和 HIF1α 基因的表达。

micro-RNAs dependent regulation of DNMT and HIF1α gene expression in thrombotic disorders.

机构信息

Defence Institute of Physiology and Allied Sciences, DRDO, Delhi, India.

Department of Biotechnology, Jamia Millia Islamia, Delhi, India.

出版信息

Sci Rep. 2019 Mar 20;9(1):4815. doi: 10.1038/s41598-018-38057-6.

DOI:10.1038/s41598-018-38057-6
PMID:30894555
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6426883/
Abstract

MicroRNAs (miRNAs) are involved in a wide variety of cellular processes and post-transcriptionally regulate several mechanism and diseases. However, contribution of miRNAs functioning during hypoxia and DNA methylation together is less understood. The current study was aimed to find a shared miRNAs signature upstream to hypoxia (via HIF gene family members) and methylation (via DNMT gene family members). This was followed by the global validation of the hypoxia related miRNA signature using miRNA microarray meta-analysis of the hypoxia induced human samples. We further concluded the study by looking into thrombosis related terms and pathways enriched during protein-protein interaction (PPI) network analysis of these two sets of gene family. Network prioritization of these shared miRNAs reveals miR-129, miR-19band miR-23b as top regulatory miRNAs. A comprehensive meta-analysis of microarray datasets of hypoxia samples revealed 29 differentially expressed miRNAs. GSEA of the interacting genes in the DNMT-HIF PPI network indicated thrombosis associated pathways including "Hemostasis", "TPO signaling pathway" and "angiogenesis". Interestingly, the study has generated a novel database of candidate miRNA signatures shared between hypoxia and methylation, and their relation to thrombotic pathways, which might aid in the development of potential therapeutic biomarkers.

摘要

微小 RNA（miRNAs）参与了广泛的细胞过程，并在后转录水平上调节了几种机制和疾病。然而，miRNAs 在缺氧和 DNA 甲基化过程中的作用的贡献还不太清楚。本研究旨在寻找一个与缺氧（通过 HIF 基因家族成员）和甲基化（通过 DNMT 基因家族成员）相关的共享 miRNA 特征。这是通过对缺氧诱导的人类样本进行 miRNA 微阵列荟萃分析，对缺氧相关 miRNA 特征进行全球验证来完成的。我们进一步通过研究血栓形成相关术语和通路，对这两组基因家族的蛋白质-蛋白质相互作用（PPI）网络分析进行了补充。这些共享 miRNA 的网络优先级分析显示 miR-129、miR-19b 和 miR-23b 是顶级调控 miRNA。对缺氧样本的微阵列数据集进行的综合荟萃分析显示，有 29 个差异表达的 miRNAs。DNMT-HIF PPI 网络中相互作用基因的 GSEA 分析表明，与血栓形成相关的通路包括“止血”、“TPO 信号通路”和“血管生成”。有趣的是，该研究生成了一个新的候选 miRNA 特征数据库，该数据库是在缺氧和甲基化之间共享的，以及它们与血栓形成通路的关系，这可能有助于开发潜在的治疗性生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ed6/6426883/f046f6eb9eb5/41598_2018_38057_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ed6/6426883/ec4d84fbcac5/41598_2018_38057_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ed6/6426883/68c8c098c232/41598_2018_38057_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ed6/6426883/dbd6e6bc3eea/41598_2018_38057_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ed6/6426883/040e356c3fc9/41598_2018_38057_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ed6/6426883/f046f6eb9eb5/41598_2018_38057_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ed6/6426883/ec4d84fbcac5/41598_2018_38057_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ed6/6426883/68c8c098c232/41598_2018_38057_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ed6/6426883/dbd6e6bc3eea/41598_2018_38057_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ed6/6426883/040e356c3fc9/41598_2018_38057_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ed6/6426883/f046f6eb9eb5/41598_2018_38057_Fig5_HTML.jpg

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