Open AccessNuclear microRNA-466c regulates Vegfa expression in response to hypoxia
Author(s) -
Pia Laitinen,
Mari-Anna Väänänen,
Ida-Liisa Kolari,
Petri Mäkinen,
Minna U. Kaikkonen,
Marc S. Weinberg,
Kevin V. Morris,
Paula Korhonen,
Tarja Malm,
Seppo YläHerttuala,
Thomas C. Roberts,
Mikko P. Turunen,
Tiia A. Turunen
Publication year - 2022
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0265948
Subject(s) - vascular endothelial growth factor a , microrna , biology , gene silencing , regulation of gene expression , gene expression , microbiology and biotechnology , rna interference , three prime untranslated region , downregulation and upregulation , transcription factor , gene , messenger rna , genetics , untranslated region , rna , vascular endothelial growth factor , cancer research , vegf receptors
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.