Autoregulation of glypican-1 by intronic microRNA-149 fine-tunes the angiogenic response to fibroblast growth factor in human endothelial cells
Abstract
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.
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The GPC1 eQTL signal may be driven by the miR-QTL effect on miR-149-5p.
“Our results together with the published findings suggest that the GPC1 eQTL signal may be driven by the miR-QTL effect on miR-149–5p and demonstrates that considering miR-QTLs can reveal the mechanism of action of host gene eQTLs.”
From Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions (2024) · cites this paper as [22]
miR-149-5p has its own intronic promoter.
“For one of these pairs, miR-149–5p and host gene GPC1, previous work has shown that the miRNA targets the host gene in endothelial cells, has its own intronic promoter, and is activated independently of the host gene22.”
From Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions (2024) · cites this paper as [22]
miR-149-5p is activated independently of host gene GPC1.
“For one of these pairs, miR-149–5p and host gene GPC1, previous work has shown that the miRNA targets the host gene in endothelial cells, has its own intronic promoter, and is activated independently of the host gene22.”
From Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions (2024) · cites this paper as [22]
miR-149-5p targets host gene GPC1 in endothelial cells.
“For one of these pairs, miR-149–5p and host gene GPC1, previous work has shown that the miRNA targets the host gene in endothelial cells, has its own intronic promoter, and is activated independently of the host gene22.”
From Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions (2024) · cites this paper as [22]
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Fernández-de Frutos, M., Galán-Chilet, I., Goedeke, L., Kim, B., Pardo-Marqués, V., Pérez-García, A., Herrero, J. I., Fernández-Hernando, C., Kim, J., & Ramírez, C. M. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00170-19 · Cited by 82 · see citing works
Vattathil, S. M., Gerasimov, E. S., Canon, S. M., Lori, A., Tan, S. S. M., Kim, P. J., Liu, Y., Lai, E. C., Bennett, D. A., Wingo, T. S., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00778-x · Cited by 14 · see citing works
- Authors
- Chamorro-Jorganes, A., Araldi, E., Rotllan, N., Cirera-Salinas, D., & Suárez, Y.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2014-01-01
- ISSN
- 1477-9137
- 0021-9533
- Cited by
- 36
- References
- 0
- Language
- en
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