Increased Expression of Angiogenic Genes in the Brains of Mouse Meg3-Null Embryos
Increased Expression of Angiogenic Genes in the Brains of Mouse Meg3-Null Embryos
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DOI：
10.1210/en.2009-1151
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发表时间：
2010-06-01
期刊：
影响因子：
4.8
通讯作者：
Klibanski, Anne
中科院分区：
文献类型：
--
作者：
Gordon, Francesca E.;Nutt, Catherine L.;Klibanski, Anne
母系表达基因3（MEG 3）是一种在正常人脑和垂体中高度表达的非编码RNA。MEG 3在促性腺激素源性临床无功能垂体腺瘤中的表达缺失产生Meg 3基因敲除小鼠以鉴定该基因在胚胎发育和肿瘤发生中的靶点和潜在功能。使用微阵列分析比较Meg 3缺失胚胎和野生型同窝对照的大脑中的基因表达谱。用GeneSifter分析微阵列数据，GeneSifter使用京都基因和基因组途径百科全书和基因本体分类来鉴定数据集中感兴趣的信号传导级联和功能类别。在野生型和基因敲除胚胎之间发现了与血管生成相关的信号通路和本体的差异。定量RTPCR和免疫组织化学染色显示，在Meg 3基因缺失的胚胎中，一些血管内皮生长因子途径基因的表达增加，皮质微血管密度增加。总之，Meg 3可能在脑血管形成的控制中发挥重要作用，并可能通过抑制血管生成部分地起到肿瘤抑制剂的作用。（内分泌学151：2443-2452，2010）
Maternally expressed gene 3 (MEG3) is a noncoding RNA highly expressed in the normal human brain and pituitary. Expression of MEG3 is lost in gonadotroph-derived clinically nonfunctioning pituitary adenomas. Meg3 knockout mice were generated to identify targets and potential functions of this gene in embryonic development and tumorigenesis. Gene expression profiles were compared in the brains of Meg3-null embryos and wild-type littermate controls using microarray analysis. Microarray data were analyzed with GeneSifter, which uses Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology classifications to identify signaling cascades and functional categories of interest within the dataset. Differences were found in signaling pathways and ontologies related to angiogenesis between wild-type and knockout embryos. Quantitative RTPCR and immunohistological staining showed increased expression of some Vascular Endothelial Growth Factor pathway genes and increased cortical microvessel density in the Meg3-null embryos. In conclusion, Meg3 may play an important role in control of vascularization in the brain and may function as a tumor suppressor in part by inhibiting angiogenesis. (Endocrinology 151: 2443-2452, 2010)