| Resumo: | MicroRNAs are well characterized in their role in silencing gene expression by targeting 3´-UTR of mRNAs in cytoplasm. However, recent studies have shown that miRNAs have a role in the regulation of genes in the nucleus, where they are abundantly located. We show here that in mouse endothelial cell line (C166), nuclear microRNA miR-466c participates in the regulation of vascular endothelial growth factor a (<i>Vegfa</i>) gene expression in hypoxia. Upregulation of <i>Vegfa</i> expression in response to hypoxia was significantly compromised after removal of miR-466c with CRISPR-Cas9 genomic deletion. We identified a promoter-associated long non-coding RNA on mouse <i>Vegfa</i> promoter and show that miR-466c directly binds to this transcript to modulate <i>Vegfa</i> expression. Collectively, these observations suggest that miR-466c regulates <i>Vegfa</i> gene transcription in the nucleus by targeting the promoter, and expands on our understanding of the role of miRNAs well beyond their canonical role.
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