title: MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that regulate gene expression at post-transcriptional level. The recent discovery of the involvement of these RNAs in the control of angiogenesis renders them very attractive in the development of new approaches for restoring the angiogenic balance. Whereas miRNA-21 has been demonstrated to be highly expressed in endothelial cells, the potential function of this miRNA in angiogenesis has never been investigated.
  
  
  RESULTS
  We first observed in endothelial cells a negative regulation of miR-21 expression by serum and bFGF, two pro-angiogenic factors. Then using in vitro angiogenic assays, we observed that miR-21 acts as a negative modulator of angiogenesis. miR-21 overexpression reduced endothelial cell proliferation, migration and the ability of these cells to form tubes whereas miR-21 inhibition using a LNA-anti-miR led to opposite effects. Expression of miR-21 in endothelial cells also led to a reduction in the organization of actin into stress fibers, which may explain the decrease in cell migration. Further mechanistic studies showed that miR-21 targets RhoB, as revealed by a decrease in RhoB expression and activity in miR-21 overexpressing cells. RhoB silencing impairs endothelial cell migration and tubulogenesis, thus providing a possible mechanism for miR-21 to inhibit angiogenesis. Finally, the therapeutic potential of miR-21 as an angiogenesis inhibitor was demonstrated in vivo in a mouse model of choroidal neovascularization.
  
  
  CONCLUSIONS
  Our results identify miR-21 as a new angiogenesis inhibitor and suggest that inhibition of cell migration and tubulogenesis is mediated through repression of RhoB.
authors.affiliation: Unit of Molecular Biology and Genetic Engineering, GIGA-Research, University of Liège, Sart Tilman, Liège, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Sabatel
authors.forename: Ludovic
authors.initials: L
authors.lastname: Malvaux
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bovy
authors.forename: Christophe
authors.initials: C
authors.lastname: Deroanne
authors.forename: Vincent
authors.initials: V
authors.lastname: Lambert
authors.forename: Maria-Luz Alvarez
authors.initials: ML
authors.lastname: Gonzalez
authors.forename: Alain
authors.initials: A
authors.lastname: Colige
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Rakic
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Martial
authors.forename: Ingrid
authors.initials: I
authors.lastname: Struman
mesh_terms: D000818:Animals; D001483:Base Sequence; D002417:Cattle; D020256:Choroidal Neovascularization / Q000201:enzymology / Q000235:genetics; D004285:Dogs; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D061307:Human Umbilical Vein Endothelial Cells / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000235:genetics*; D051381:Rats; D020743:rhoB GTP-Binding Protein / Q000235:genetics*
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D020743:rhoB GTP-Binding Protein