Autoregulation of glypican-1 by intronic microRNA-149 fine-tunes the angiogenic response to fibroblast growth factor in human endothelial cells
Copyright policy )Autoregulation of glypican-1 by intronic microRNA-149 fine-tunes the angiogenic response to fibroblast growth factor in human endothelial cells
MiR-149 is located within the first intron of glypican-1 (GPC1) gene. GPC1 is low affinity receptor for fibroblast growth factor (FGF2) that favors FGF2- binding to its receptor (FGFR1), subsequently promoting FGF2-FGFR1 activation and signaling. Using bioinformatic approaches, both GPC1 and FGFR1 were identified and subsequently validated as targets for miR-149 (both mature and passenger strands) in endothelial cells (ECs). ?As a consequence of their targeting activity towards GPC1 and FGFR1, both miR-149 and miR-149* regulated FGF2 signaling and FGF2-induced responses in ECs, namely proliferation, migration and cord formation. Moreover, lentiviral overexpression of miR-149 reduced in vivo tumor-induced neovascularization. Importantly, FGF2 transcriptionally stimulated the expression of miR-149 independently of its host gene, therefore assuring the steady state of FGF2-induced responses through the regulation of the GPC1-FGFR1 binary complex in ECs.
- New York University United States
- Leibniz Association Germany
- Yale University United States
- University of Parma Italy
- German Rheumatism Research Centre Germany
Male, 570, FGF2, Gene Expression, Neovascularization, Physiologic, Carcinoma, Lewis Lung, Mice, Endothelial cell, Glypicans, Human Umbilical Vein Endothelial Cells, Animals, Humans, Receptor, Fibroblast Growth Factor, Type 1, Cells, Cultured, microRNA, Neovascularization, Pathologic, MiR-149*Angiogenesis, 500, MicroRNAs, Fibroblast Growth Factor 2, RNA Interference, Glypican-1, Neoplasm Transplantation, Signal Transduction
Male, 570, FGF2, Gene Expression, Neovascularization, Physiologic, Carcinoma, Lewis Lung, Mice, Endothelial cell, Glypicans, Human Umbilical Vein Endothelial Cells, Animals, Humans, Receptor, Fibroblast Growth Factor, Type 1, Cells, Cultured, microRNA, Neovascularization, Pathologic, MiR-149*Angiogenesis, 500, MicroRNAs, Fibroblast Growth Factor 2, RNA Interference, Glypican-1, Neoplasm Transplantation, Signal Transduction
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