Yin Runting, Wang Rubing, Guo Le, Zhang Wei, Lu Yong
Department of Pharmacology, Nantong University Medical College, Nantong, PR China.
J Vasc Res. 2013;50(2):157-66. doi: 10.1159/000345697. Epub 2012 Dec 21.
MicroRNAs (miRs) are endogenously expressed small noncoding RNAs that regulate gene expression at the posttranscriptional level. Previous works indicated that the miR-17-92 cluster could regulate endothelial cell (EC) functions involved in angiogenesis. miR-17-3p, a component of the miR-17-92 cluster, could control the angiogenic activity of human umbilical vein ECs in a cell-autonomous manner in vitro. A 21-bp fragment from the Flk-1 3'-untranslated region containing miR-17-3p targeting sites was required for the rapid downregulation of Flk-1 expression by in silico and experimental analysis. Subsequently, the downstream cell growth pathway was inhibited by forced upregulation of miR-17-3p. Based on these data, we conclude that miR-17-3p is a negative regulator of the angiogenic phenotype of ECs through its ability to modulate the expression of Flk-1, which is implicated in the pleiotropic effects of miR-17-92 in angiogenesis.
微小RNA（miRs）是内源性表达的小非编码RNA，可在转录后水平调节基因表达。先前的研究表明，miR-17-92簇可调节参与血管生成的内皮细胞（EC）功能。miR-17-3p是miR-17-92簇的一个组成部分，在体外可通过细胞自主方式控制人脐静脉内皮细胞的血管生成活性。通过计算机模拟和实验分析，发现来自Flk-1 3'-非翻译区的一个含miR-17-3p靶向位点的21碱基片段是Flk-1表达快速下调所必需的。随后，miR-17-3p的强制上调抑制了下游细胞生长途径。基于这些数据，我们得出结论，miR-17-3p通过调节Flk-1的表达，是内皮细胞血管生成表型的负调节因子，这与miR-17-92在血管生成中的多效性作用有关。
