A regulatory microRNA network controls endothelial cell phenotypic switch during sprouting angiogenesis

Stefania Rosano, Davide Corà, Sushant Parab, Serena Zaffuto, Claudio Isella, Roberta Porporato, Roxana Maria Hoza, Raffaele A Calogero, Chiara Riganti, Federico Bussolino, Alessio Noghero

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Publication statusPublished - Jan 24 2020


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