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长链非编码 RNA 在缺血后心脏中的表达谱和本体分析及其在缺血/再灌注损伤中的潜在作用。

Expression profiling and ontology analysis of long noncoding RNAs in post-ischemic heart and their implied roles in ischemia/reperfusion injury.

机构信息

The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang Province, China; Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, PR China.

Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, PR China.

出版信息

Gene. 2014 Jun 10;543(1):15-21. doi: 10.1016/j.gene.2014.04.016. Epub 2014 Apr 12.

DOI:10.1016/j.gene.2014.04.016
PMID:24726549
Abstract

Long noncoding RNAs (lncRNAs) play important regulatory roles in cellular physiology. The contributions of lncRNAs to ischemic heart disease remain largely unknown. The aim of this study was to investigate the profile of myocardial lncRNAs and their potential roles at early stage of reperfusion. lncRNAs and mRNAs were profiled by microarray and the expression of some highly-dysregulated lncRNAs was further validated using polymerase chain reaction. Our results revealed that 64 lncRNAs were up-regulated and 87 down-regulated, while 50 mRNAs were up-regulated and 60 down-regulated in infarct region at all reperfusion sampled. Gene ontology analysis indicated that dysregulated transcripts were associated with immune response, spermine catabolic process, taxis, chemotaxis, polyamine catabolic process, spermine metabolic process, chemokine activity and chemokine receptor binding. Target gene-related pathway analysis showed significant changes in cytokine-cytokine receptor interaction, the chemokine signaling pathway and nucleotide oligomerization domain (NOD)-like receptor signaling pathway which have a close relationship with myocardial ischemia/reperfusion injury (MI/RI). Besides, a gene co-expression network was constructed to identify correlated targets of 10 highly-dysregulated lncRNAs. These lncRNAs may play their roles by this network in post-ischemic heart. Such results provide a foundation for understanding the roles and mechanisms of myocardial lncRNAs at early stage of reperfusion.

摘要

长链非编码 RNA(lncRNA)在细胞生理中发挥重要的调节作用。lncRNA 对缺血性心脏病的贡献在很大程度上仍然未知。本研究旨在探讨再灌注早期心肌 lncRNA 的特征及其潜在作用。通过微阵列对 lncRNA 和 mRNA 进行了分析,并使用聚合酶链反应进一步验证了一些高度失调的 lncRNA 的表达。我们的结果表明,在所有再灌注取样的梗死区域中,有 64 个 lncRNA 上调,87 个 lncRNA 下调,而 50 个 mRNA 上调,60 个 mRNA 下调。基因本体分析表明,失调的转录物与免疫反应、精胺分解代谢过程、趋化性、趋化性、多胺分解代谢过程、精胺代谢过程、趋化因子活性和趋化因子受体结合有关。靶基因相关通路分析显示,细胞因子-细胞因子受体相互作用、趋化因子信号通路和核苷酸寡聚化结构域(NOD)样受体信号通路发生显著变化,这些通路与心肌缺血/再灌注损伤(MI/RI)密切相关。此外,构建了一个基因共表达网络,以识别 10 个高度失调的 lncRNA 的相关靶基因。这些 lncRNA 可能通过该网络在缺血后心脏中发挥作用。这些结果为理解再灌注早期心肌 lncRNA 的作用和机制提供了基础。

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