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

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.

• Authors: 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, Tiia A Turunen
• Journal: PloS one (PLoS One) Vol. 17 Issue 3 Pg. e0265948 ( 2022) ISSN: 1932-6203 [Electronic] United States
• PMID: 35358280 (Publication Type: Journal Article)

Chemical References

• MicroRNAs
• Mirn466 microRNA, mouse
• RNA, Long Noncoding
• RNA, Messenger
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse

Topics

• Animals
• Hypoxia (genetics)
• Mice
• MicroRNAs (genetics)
• RNA, Long Noncoding (genetics)
• RNA, Messenger
• Vascular Endothelial Growth Factor A (metabolism)