Nuclear microRNA-466c regulates Vegfa expression in response to hypoxia

Pia Laitinen, Mari-Anna Väänänen, Ida-Liisa Kolari, Petri I Mäkinen, Minna U Kaikkonen, Marc S Weinberg, Kevin V Morris, Paula Korhonen, Tarja Malm, Seppo Ylä-Herttuala, Thomas C Roberts, Mikko P Turunen and Tiia A Turunen

PLOS ONE, 2022, vol. 17, issue 3, 1-18

Abstract: 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 (Vegfa) gene expression in hypoxia. Upregulation of Vegfa 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 Vegfa promoter and show that miR-466c directly binds to this transcript to modulate Vegfa expression. Collectively, these observations suggest that miR-466c regulates Vegfa gene transcription in the nucleus by targeting the promoter, and expands on our understanding of the role of miRNAs well beyond their canonical role.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0265948

DOI: 10.1371/journal.pone.0265948

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