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MicroRNA miR-214-5p induces senescence of microvascular endothelial cells by targeting the JAG1/Notch signaling pathway

During cellular senescence, irreversible cell cycle arrest is accompanied by morphological and genetic alterations. MicroRNAs (miRNAs) play a critical role in regulating senescence by modulating the abundance of crucial senescence regulatory proteins. Therefore, to identify novel senescence-associat...

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Detalles Bibliográficos
Autores principales: Jo, Hye-ram, Hwang, Jiwon, Jeong, Jae-Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227379/
https://www.ncbi.nlm.nih.gov/pubmed/37260583
http://dx.doi.org/10.1016/j.ncrna.2023.05.002
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author Jo, Hye-ram
Hwang, Jiwon
Jeong, Jae-Hoon
author_facet Jo, Hye-ram
Hwang, Jiwon
Jeong, Jae-Hoon
author_sort Jo, Hye-ram
collection PubMed
description During cellular senescence, irreversible cell cycle arrest is accompanied by morphological and genetic alterations. MicroRNAs (miRNAs) play a critical role in regulating senescence by modulating the abundance of crucial senescence regulatory proteins. Therefore, to identify novel senescence-associated miRNAs, we analyzed differentially expressed miRNAs in microvascular endothelial cells (MVEC). Among the 80 differentially expressed miRNAs in replicative senescent MVECs, 16 miRNAs of unknown gene ontology were used in the senescence-associated β-galactosidase assay. Thus, we identified miR-214-5p as having high senescence-inducing activity, inhibiting the proliferation and angiogenesis activity of MVECs. To reveal the senescence-regulating mechanism of miR-214-5p, we searched for target genes through sequence- and literature-based analysis. Molecular manipulation of miR-214-5p demonstrated that miR-214-5p regulated the expression and function of Jagged 1 (JAG1) in senescent MVECs. Silencing JAG1 or downstream genes of JAG1-Notch signaling, accelerated the senescence of MVECs. Additionally, ectopic overexpression of JAG1 reversed the senescence-inducing activity of miR-214-5p. In conclusion, we identified miR-214-5p as a senescence-associated miRNA. Targeting miR-214-5p may be a potential strategy to delay vascular aging and overcome the detrimental effects of senescence and age-related diseases.
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spelling pubmed-102273792023-05-31 MicroRNA miR-214-5p induces senescence of microvascular endothelial cells by targeting the JAG1/Notch signaling pathway Jo, Hye-ram Hwang, Jiwon Jeong, Jae-Hoon Noncoding RNA Res Original Research Article During cellular senescence, irreversible cell cycle arrest is accompanied by morphological and genetic alterations. MicroRNAs (miRNAs) play a critical role in regulating senescence by modulating the abundance of crucial senescence regulatory proteins. Therefore, to identify novel senescence-associated miRNAs, we analyzed differentially expressed miRNAs in microvascular endothelial cells (MVEC). Among the 80 differentially expressed miRNAs in replicative senescent MVECs, 16 miRNAs of unknown gene ontology were used in the senescence-associated β-galactosidase assay. Thus, we identified miR-214-5p as having high senescence-inducing activity, inhibiting the proliferation and angiogenesis activity of MVECs. To reveal the senescence-regulating mechanism of miR-214-5p, we searched for target genes through sequence- and literature-based analysis. Molecular manipulation of miR-214-5p demonstrated that miR-214-5p regulated the expression and function of Jagged 1 (JAG1) in senescent MVECs. Silencing JAG1 or downstream genes of JAG1-Notch signaling, accelerated the senescence of MVECs. Additionally, ectopic overexpression of JAG1 reversed the senescence-inducing activity of miR-214-5p. In conclusion, we identified miR-214-5p as a senescence-associated miRNA. Targeting miR-214-5p may be a potential strategy to delay vascular aging and overcome the detrimental effects of senescence and age-related diseases. KeAi Publishing 2023-05-18 /pmc/articles/PMC10227379/ /pubmed/37260583 http://dx.doi.org/10.1016/j.ncrna.2023.05.002 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research Article
Jo, Hye-ram
Hwang, Jiwon
Jeong, Jae-Hoon
MicroRNA miR-214-5p induces senescence of microvascular endothelial cells by targeting the JAG1/Notch signaling pathway
title MicroRNA miR-214-5p induces senescence of microvascular endothelial cells by targeting the JAG1/Notch signaling pathway
title_full MicroRNA miR-214-5p induces senescence of microvascular endothelial cells by targeting the JAG1/Notch signaling pathway
title_fullStr MicroRNA miR-214-5p induces senescence of microvascular endothelial cells by targeting the JAG1/Notch signaling pathway
title_full_unstemmed MicroRNA miR-214-5p induces senescence of microvascular endothelial cells by targeting the JAG1/Notch signaling pathway
title_short MicroRNA miR-214-5p induces senescence of microvascular endothelial cells by targeting the JAG1/Notch signaling pathway
title_sort microrna mir-214-5p induces senescence of microvascular endothelial cells by targeting the jag1/notch signaling pathway
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227379/
https://www.ncbi.nlm.nih.gov/pubmed/37260583
http://dx.doi.org/10.1016/j.ncrna.2023.05.002
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