Department of Pathology and Laboratory Medicine, Center for Vascular Biology, Weill Cornell Medical College, Cornell University, New York, New York, USA.
Curr Opin Hematol. 2014 May;21(3):235-40. doi: 10.1097/MOH.0000000000000040.
This review summarizes recent findings in the area of post-transcriptional regulation of gene expression during angiogenesis, also known as new blood vessel formation. Specifically, we focus on gene regulation by HuR, an RNA-binding protein (RBP), and microRNAs (miRNAs) and their interplay, which ultimately influences cellular phenotypes of cells involved in angiogenesis.
Recently, RBPs and miRNAs have emerged as key regulators of angiogenesis. We and others have demonstrated that the RBP HuR (a.k.a. Elavl1) stabilizes vascular endothelial growth factor-A mRNA, a potent angiogenic factor in the settings of tumor development and inflammation. However, several miRNAs were shown to modulate gene expression during developmental (miR-126), physiological (miR-126, miR-92a), and pathological angiogenesis (miR-200b, miR-132). Moreover, the interplay of HuR and miRNAs in the regulation of genes involved in angiogenesis was described. In addition, recent work suggests a new role of circulating miRNAs as paracrine mediators in angiogenesis.
The elucidation of novel posttranscriptional gene regulatory mechanisms has expanded our understanding of angiogenesis in physiological and pathological conditions. We anticipate that this knowledge will ultimately lead to new insights for discovering novel therapeutic strategies to control pathological angiogenesis.
本文总结了血管生成（即新血管形成）过程中转录后基因表达调控的最新研究发现。具体而言，我们重点关注 RNA 结合蛋白 (RBP) HuR 和 microRNAs (miRNAs) 及其相互作用对参与血管生成的细胞表型的影响。
最近，RBP 和 miRNAs 已成为血管生成的关键调控因子。我们和其他人已经证明，RBP HuR（也称为 Elavl1）稳定了血管内皮生长因子-A mRNA，这是肿瘤发展和炎症环境中一种强大的血管生成因子。然而，一些 miRNAs 被证明在发育（miR-126）、生理（miR-126、miR-92a）和病理性血管生成（miR-200b、miR-132）过程中调节基因表达。此外，还描述了 HuR 和 miRNAs 在调节血管生成相关基因中的相互作用。此外，最近的研究工作表明，循环 miRNAs 作为旁分泌介体在血管生成中具有新的作用。
新的转录后基因调控机制的阐明扩展了我们对生理和病理条件下血管生成的理解。我们预计，这些知识最终将为发现控制病理性血管生成的新治疗策略提供新的见解。
