Distinct RNA transcriptome patterns are potentially associated with angiogenesis in Tie2-expressing monocytes

Distinct RNA transcriptome patterns are potentially associated with angiogenesis in Tie2-expressing monocytes
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独特的 RNA 转录组模式可能与表达 Tie2 的单核细胞中的血管生成相关

DOI:
10.1016/j.gene.2015.12.065
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发表时间:
2016-04-10
期刊:
影响因子:
3.5
通讯作者:
Wang, Xipeng
Wang, Xipeng
中科院分区:
生物学3区
文献类型:
--
作者:
Wang, Xinjing;Dai, Zhiyuan;Wang, Xipeng

文献摘要

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表达Tie2的单核细胞(TEM)先前被鉴定为单核细胞的新亚群,并且被认为在人类肿瘤中具有突出的促血管生成活性。但TEM促血管生成的分子机制尚不清楚。RNA转录组模式包括非编码RNA(microRNA,miRNA)和长链非编码RNA(longnoncodingRNA,IncRNA),在细胞分化和功能中起着重要作用。然而,对TEM的转录组模式知之甚少,包括那些非编码RNA。我们使用Agilent Human miRNA(8 * 60K,Design ID:046064)微阵列和Agilent IncRNA Gene Expression(4 * 180K,Design ID:042818)微阵列探索TEM和不表达Tie2的匹配单核细胞(Tie2(-)单核细胞)的转录组,所述单核细胞分离自健康成人的外周血。与Tie2(-)单核细胞相比,TEM中共发现141种mRNA、142种IncRNA和75种miRNA表达异常。根据系统聚类分析,TEM具有不同的RNA转录组模式,然后通过实时定量逆转录聚合酶链反应(qRT-PCR)确认基因表达模式。基因本体(Gene Ontology,GO)功能注释分析表明,TEMs中上调的mRNA与血管重塑和上皮细胞增殖的正向调节有关,上调的胰岛素样生长因子1(insulin like growth factor 1,IGF1)mRNA参与了这两条途径。为了对这些失调的非编码RNA进行功能分析,预测了miRNAs的靶基因,并进行了IncRNA的顺式/反式调节分析。(C)2016爱思唯尔B.V.保留所有权利。
Tie2-expressing Monocytes (TEMs) were previously identified as a novel subset of monocytes and were believed to have prominent pro-angiogenesis activities in human tumors. While the molecular mechanism of the angiogenesis promoting capacity of TEMs remains unclear. RNA transcriptome pattern, including non-coding RNAs as microRNA (miRNA) and long non-coding RNA (IncRNA), plays important role in cell differentiation and functions. However, little is known about the transcriptome patterns of TEMs, including those non-coding RNAs. We explore the transcriptome of TEMs and the matched monocytes that do not express Tie2 (Tie2(-) monocytes) isolated from peripheral blood of healthy adults employing the Agilent Human miRNA(8*60K,Design ID: 046064)microarray and the Agilent IncRNA Gene Expression(4*180K, Design ID: 042818)microarray. A total of 141 mRNAs, 142 IncRNAs and 75 miRNAs were found dysregulated in TEMs compared to Tie2(-) monocytes. TEMs have the distinct RNA transcriptome patterns according to the Hierarchical clustering and then the gene expression patterns were confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Functional annotation by Gene Ontology (GO) analyses showed that the up-regulated mRNAs in TEMs were associated to blood vessel remodeling and positive regulation of epithelial cell proliferation, and the up-regulated insulin like growth factor 1 (IGF1) mRNA was involved in both pathways. For functional analysis of those dysregulated non-coding RNAs, target genes of the miRNAs were predicted and cis/trans-regulation analysis of the IncRNAs were performed. (C) 2016 Elsevier B.V. All rights reserved.