title: miR126-5p repression of ALCAM and SetD5 in endothelial cells regulates leucocyte adhesion and transmigration.
abstract: OBJECTIVE
  miR126-5p is processed from the miR126-3p/-5p duplex, which is expressed in endothelial cells and gives rise to the guide strand miR126-3p and the passenger strand miR126-5p. miR126-3p has prominent roles in vascular development and diseases, whereas the expression and physiological functions of miR126-5p are unknown. The purpose of this study was to evaluate the expression and role of miR126-5p in blood vessel endothelial cells.
  
  
  RESULTS
  miR126-5p is mostly expressed in blood vessel endothelial cells in vivo and in vitro. Gain- and loss-of-function approaches revealed that miR126-5p promotes leucocyte adhesion and represses leucocyte transendothelial migration. Two distinct target genes of miR126-5p in endothelial cells were identified: the activated leucocyte cell adhesion molecule (ALCAM) gene which codes for an adhesion molecule involved in leucocyte transendothelial migration and SetD5, a gene with previously unknown functions. Using either a blocking antibody or target protectors which specifically disrupt the miRNA/mRNA target pairing, we showed that miR126-5p promotes leucocyte adhesion by controlling the expression of SetD5 and represses transendothelial migration via the regulation of ALCAM. miR126-5p controls ALCAM and SetD5 expression in vivo in separate tissues and regulates leucocyte infiltration into inflamed lungs by repressing ALCAM expression.
  
  
  CONCLUSIONS
  miR126-5p is a functional, endothelial-enriched microRNA that participates in the control of leucocyte trafficking by regulating the expression of ALCAM and SetD5.
authors.affiliation: CNRS, UMR8161, Institut de Biologie de Lille, Institut Pasteur de Lille, Université Lille-Nord de France, 1 rue du Pr Calmette, Lille Cedex 59021, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Poissonnier
authors.affiliation: CNRS, UMR8161, Institut de Biologie de Lille, Institut Pasteur de Lille, Université Lille-Nord de France, 1 rue du Pr Calmette, Lille Cedex 59021, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Villain
authors.affiliation: CNRS, UMR8161, Institut de Biologie de Lille, Institut Pasteur de Lille, Université Lille-Nord de France, 1 rue du Pr Calmette, Lille Cedex 59021, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Soncin
authors.affiliation: CNRS, UMR8161, Institut de Biologie de Lille, Institut Pasteur de Lille, Université Lille-Nord de France, 1 rue du Pr Calmette, Lille Cedex 59021, France virginie.mattot@ibl.fr.
authors.forename: Virginie
authors.initials: V
authors.lastname: Mattot
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D005326:Fetal Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D008780:Methyltransferases / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D015703:Antigens, CD; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D008780:Methyltransferases; D035683:MicroRNAs; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C527111:MIRN126 microRNA, human; C545201:MIRN126 microRNA, mouse; C000588437:SETD5 protein, human
keywords: Endothelium; Leucocyte trafficking; miR126-5p; miRNA