1. A regulatory microRNA network controls endothelial cell phenotypic switch during sprouting angiogenesis.
- Author
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Rosano S, Corà D, Parab S, Zaffuto S, Isella C, Porporato R, Hoza RM, Calogero RA, Riganti C, Bussolino F, and Noghero A
- Subjects
- Angiogenesis Inhibitors pharmacology, Angiogenesis Inhibitors therapeutic use, Biomarkers, Tumor, Cells, Cultured, Colorectal Neoplasms drug therapy, Gene Expression Regulation, Neoplastic drug effects, Human Umbilical Vein Endothelial Cells, Humans, Phenotype, Endothelial Cells cytology, Endothelial Cells physiology, MicroRNAs genetics, MicroRNAs metabolism, Neovascularization, Pathologic metabolism, Neovascularization, Physiologic genetics, Neovascularization, Physiologic physiology
- Abstract
Angiogenesis requires the temporal coordination of the proliferation and the migration of endothelial cells. Here, we investigated the regulatory role of microRNAs (miRNAs) in harmonizing angiogenesis processes in a three-dimensional in vitro model. We described a microRNA network which contributes to the observed down- and upregulation of proliferative and migratory genes, respectively. Global analysis of miRNA-target gene interactions identified two sub-network modules, the first organized in upregulated miRNAs connected with downregulated target genes and the second with opposite features. miR-424-5p and miR-29a-3p were selected for the network validation. Gain- and loss-of-function approaches targeting these microRNAs impaired angiogenesis, suggesting that these modules are instrumental to the temporal coordination of endothelial migration and proliferation. Interestingly, miR-29a-3p and its targets belong to a selective biomarker that is able to identify colorectal cancer patients who are responding to anti-angiogenic treatments. Our results provide a view of higher-order interactions in angiogenesis that has potential to provide diagnostic and therapeutic insights., Competing Interests: SR, DC, SP, SZ, CI, RP, RH, RC, CR, FB, AN No competing interests declared, (© 2020, Rosano et al.)
- Published
- 2020
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