Wang Xinjing, Dai Zhiyuan, Wu Xiaoli, Wang Kai, Wang Xipeng
Shanghai First Maternity and Infant Hospital, Tongji University, School of Medicine.
Gene. 2016 Apr 10;580(1):1-7. doi: 10.1016/j.gene.2015.12.065. Epub 2015 Dec 31.
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 (lncRNA), 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(860K,Design ID: 046064)microarray and the Agilent lncRNA Gene Expression(4180K, Design ID: 042818)microarray. A total of 141 mRNAs, 142 lncRNAs 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 lncRNAs were performed.
表达Tie2的单核细胞（TEMs）先前被鉴定为单核细胞的一个新亚群，并且被认为在人类肿瘤中具有显著的促血管生成活性。然而，TEMs促血管生成能力的分子机制仍不清楚。RNA转录组模式，包括作为微小RNA（miRNA）和长链非编码RNA（lncRNA）的非编码RNA，在细胞分化和功能中起重要作用。然而，关于TEMs的转录组模式，包括那些非编码RNA，所知甚少。我们使用安捷伦人类miRNA（8×60K，设计ID：046064）微阵列和安捷伦lncRNA基因表达（4×180K，设计ID：042818）微阵列，探索从健康成年人外周血中分离出的TEMs和不表达Tie2的匹配单核细胞（Tie2（-）单核细胞）的转录组。与Tie2（-）单核细胞相比，共发现141种mRNA、142种lncRNA和75种miRNA在TEMs中表达失调。根据层次聚类，TEMs具有独特的RNA转录组模式，然后通过定量实时逆转录聚合酶链反应（qRT-PCR）确认基因表达模式。基因本体（GO）分析的功能注释表明，TEMs中上调的mRNA与血管重塑和上皮细胞增殖的正调控相关，上调的胰岛素样生长因子1（IGF1）mRNA参与了这两种途径。为了对那些失调的非编码RNA进行功能分析，预测了miRNA的靶基因，并对lncRNA进行了顺式/反式调控分析。
