miR-137 regulates the migration of human umbilical vein endothelial cells by targeting ephrin-type A receptor 7.

MicroRNAs (miRNAs) are short non-coding RNAs, which negatively regulate gene expression. Post‑transcriptional regulation by miRNAs is important for organism development. In addition, endothelial cells are key regulators of angiogenesis. By using the 3-(4,5-dimethylthiazol-2-yl)‑2,5‑diphenyltetrazolium bromide (MTT), migration and gelatin sponge-chorioallantoic membrane assays, it was demonstrated that when miR-137 was overexpressed, cell viability and migration decreased. In addition, it was observed that blocking endogenous miR-137 increased cell viability and migration. Bioinformatics analysis indicated that the 3'‑untranslated region (3'UTR) of the ephrin type-A receptor 7 (EPHA7) has a putative binding site for miR-137. miR-137 is able to directly bind to the EPHA7 3'UTR and negatively regulate the expression of EPHA7. miR-137 is also able to decrease the growth and migration of human umbilical vein endothelial cells (HUVECs). The identification of the function of miR-137 and its target gene EPHA7 in HUVECs may provide novel insights into the mechanisms of angiogenesis.

[1]  S. Miyaki,et al.  Angiogenic microRNA‐210 is present in cells surrounding osteonecrosis , 2012, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[2]  T. Dønnem,et al.  MicroRNA Signatures in Tumor Tissue Related to Angiogenesis in Non-Small Cell Lung Cancer , 2012, PloS one.

[3]  D. Hu,et al.  Epigenetics, microRNAs, and carcinogenesis: functional role of microRNA-137 in uveal melanoma. , 2011, Investigative ophthalmology & visual science.

[4]  Stefanie Dimmeler,et al.  MicroRNA-92a Controls Angiogenesis and Functional Recovery of Ischemic Tissues in Mice , 2009, Science.

[5]  Y. Suárez,et al.  MicroRNAs as novel regulators of angiogenesis. , 2009, Circulation research.

[6]  R. Weissleder,et al.  miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. , 2008, Cancer cell.

[7]  Fabio Martelli,et al.  MicroRNA-210 Modulates Endothelial Cell Response to Hypoxia and Inhibits the Receptor Tyrosine Kinase Ligand Ephrin-A3* , 2008, Journal of Biological Chemistry.

[8]  Joshua T. Mendell,et al.  MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1 , 2008, Proceedings of the National Academy of Sciences.

[9]  E. Izaurralde,et al.  Getting to the Root of miRNA-Mediated Gene Silencing , 2008, Cell.

[10]  Reuven Agami,et al.  Regulation of the p27Kip1 tumor suppressor by miR‐221 and miR‐222 promotes cancer cell proliferation , 2007 .

[11]  Stefanie Dimmeler,et al.  Role of Dicer and Drosha for Endothelial MicroRNA Expression and Angiogenesis , 2007, Circulation research.

[12]  Jordan S. Pober,et al.  Dicer Dependent MicroRNAs Regulate Gene Expression and Functions in Human Endothelial Cells , 2007, Circulation research.

[13]  Laura Mariani,et al.  MicroRNAs modulate the angiogenic properties of HUVECs. , 2006, Blood.

[14]  Marco Presta,et al.  The gelatin sponge–chorioallantoic membrane assay , 2006, Nature Protocols.

[15]  Peter Carmeliet,et al.  VEGF as a Key Mediator of Angiogenesis in Cancer , 2005, Oncology.

[16]  M. Greenberg,et al.  Regulation of EphA4 Kinase Activity Is Required for a Subset of Axon Guidance Decisions Suggesting a Key Role for Receptor Clustering in Eph Function , 2005, Neuron.

[17]  T. Hunter,et al.  Coexpressed EphA Receptors and Ephrin-A Ligands Mediate Opposing Actions on Growth Cone Navigation from Distinct Membrane Domains , 2005, Cell.

[18]  George E. Sandusky,et al.  Dicer Is Required for Embryonic Angiogenesis during Mouse Development* , 2005, Journal of Biological Chemistry.

[19]  Chad A. Cowan,et al.  Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development. , 2004, Developmental biology.

[20]  Philippe Soriano,et al.  Ephrin-B1 forward and reverse signaling are required during mouse development. , 2004, Genes & development.

[21]  K M Higgins,et al.  Loss of Eph-receptor expression correlates with loss of cell adhesion and chondrogenic capacity in Hoxa13 mutant limbs. , 2001, Development.

[22]  M. Fishman,et al.  Morphogenesis of prechordal plate and notochord requires intact Eph/ephrin B signaling. , 2001, Developmental biology.

[23]  E. Pasquale,et al.  The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization , 2000, Oncogene.

[24]  David J. Anderson,et al.  Molecular Distinction and Angiogenic Interaction between Embryonic Arteries and Veins Revealed by ephrin-B2 and Its Receptor Eph-B4 , 1998, Cell.

[25]  P. Chambon,et al.  The expression pattern of the mouse receptor tyrosine kinase gene MDK1 is conserved through evolution and requires Hoxa-2 for rhombomere-specific expression in mouse embryos. , 1996, Developmental biology.

[26]  A. Ullrich,et al.  Identification of alternatively spliced mRNAs encoding variants of MDK1, a novel receptor tyrosine kinase expressed in the murine nervous system. , 1995, Oncogene.