Nuclear microRNA-466c regulates Vegfa expression in response to hypoxia
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...
| Main Authors: | , , , , , , , , , , , , |
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| פורמט: | Journal article |
| שפה: | English |
| יצא לאור: |
Public Library of Science
2022
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| _version_ | 1826311287398727680 |
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| author | Laitinen, P Väänänen, M-A Kolari, I-L Mäkinen, PI Kaikkonen, MU Weinberg, MS Morris, KV Korhonen, P Malm, T Ylä-Herttuala, S Roberts, TC Turunen, MP Turunen, TA |
| author_facet | Laitinen, P Väänänen, M-A Kolari, I-L Mäkinen, PI Kaikkonen, MU Weinberg, MS Morris, KV Korhonen, P Malm, T Ylä-Herttuala, S Roberts, TC Turunen, MP Turunen, TA |
| author_sort | Laitinen, P |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T08:07:38Z |
| format | Journal article |
| id | oxford-uuid:19d5482c-1e17-4120-a775-31fd096c79c5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:07:38Z |
| publishDate | 2022 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:19d5482c-1e17-4120-a775-31fd096c79c52023-11-08T16:14:01ZNuclear microRNA-466c regulates Vegfa expression in response to hypoxiaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:19d5482c-1e17-4120-a775-31fd096c79c5EnglishSymplectic ElementsPublic Library of Science2022Laitinen, PVäänänen, M-AKolari, I-LMäkinen, PIKaikkonen, MUWeinberg, MSMorris, KVKorhonen, PMalm, TYlä-Herttuala, SRoberts, TCTurunen, MPTurunen, TAMicroRNAs 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. |
| spellingShingle | Laitinen, P Väänänen, M-A Kolari, I-L Mäkinen, PI Kaikkonen, MU Weinberg, MS Morris, KV Korhonen, P Malm, T Ylä-Herttuala, S Roberts, TC Turunen, MP Turunen, TA Nuclear microRNA-466c regulates Vegfa expression in response to hypoxia |
| title | Nuclear microRNA-466c regulates Vegfa expression in response to hypoxia |
| title_full | Nuclear microRNA-466c regulates Vegfa expression in response to hypoxia |
| title_fullStr | Nuclear microRNA-466c regulates Vegfa expression in response to hypoxia |
| title_full_unstemmed | Nuclear microRNA-466c regulates Vegfa expression in response to hypoxia |
| title_short | Nuclear microRNA-466c regulates Vegfa expression in response to hypoxia |
| title_sort | nuclear microrna 466c regulates vegfa expression in response to hypoxia |
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