C URRENT O PINION Post-transcriptional gene regulation by HuR and microRNAs in angiogenesis Sung-Hee Chang and Timothy Hla Purpose of review 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. Recent findings 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. Summary 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. Keywords angiogenesis, Elavl1, endothelial cells, HuR, microRNA INTRODUCTION Angiogenesis, the process by which new blood vessels develop from a preexisting vasculature, is a fundamental process required for embryonic development, postnatal physiological processes such as reproduction, wound healing, as well as pathological processes such as chronic inflam- mation, tissue responses to ischemia, and cancer [1,2]. During embryonic development, endothelial cell progenitors generate a primitive vascular network by a process called vasculogenesis, and subsequent sprouting angiogenesis is responsible for the formation of the embryonic vascular networks. It is also the latter process of sprouting angiogenesis that is responsible for most postnatal neo-vessel growth, which occurs in response to physiological demands as well as during patho- logical conditions such as cancer and chronic inflammatory diseases. Once the new vasculature is established, the endothelium returns to quiescence and thereby maintains physiological homeostasis. During physiological angiogenesis, stimuli such as hypoxia trigger a highly orchestrated process of angiogenesis, which is described below. Activated endothelium undergoes vessel sprouting, endo- thelial cell proliferation, and directed migration, leading to the formation of vascular sprouts, which ultimately fuse to form vascular networks. Nascent vessels, which become stabilized by blood flow and pericyte coverage, allow efficient blood flow and therefore tissue perfusion. Further maturation Department of Pathology and Laboratory Medicine, Center for Vascular Biology,Weill Cornell Medical College, Cornell University, New York, New York, USA Correspondence to Timothy Hla, Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Room A607E, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, New York 10021, USA. Tel: +1 212 746 9953; e-mail: tih2002@ med.cornell.edu Curr Opin Hematol 2014, 21:235–240 DOI:10.1097/MOH.0000000000000040 1065-6251 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins www.co-hematology.com REVIEW