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Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury
The miRNA-181 (miR-181) family regulates neuronal persistence during cerebral ischemia/reperfusion injury (CI/RI). Since the effect of miR-181d on CI/RI has never been studied, the current work sought to determine the involvement of miR-181d in neuronal apoptosis after brain I/R injury. To replicate...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990210/ https://www.ncbi.nlm.nih.gov/pubmed/36882763 http://dx.doi.org/10.1186/s12944-023-01794-3 |
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author | Li, Shengnan Chen, Shaofeng Wang, Yajun Hu, Xingjuan Wang, Ying Wu, Zhaochun Huang, Shaoting He, Jiawen Deng, Fu Zhao, Bin Ma, Guoda Li, You |
author_facet | Li, Shengnan Chen, Shaofeng Wang, Yajun Hu, Xingjuan Wang, Ying Wu, Zhaochun Huang, Shaoting He, Jiawen Deng, Fu Zhao, Bin Ma, Guoda Li, You |
author_sort | Li, Shengnan |
collection | PubMed |
description | The miRNA-181 (miR-181) family regulates neuronal persistence during cerebral ischemia/reperfusion injury (CI/RI). Since the effect of miR-181d on CI/RI has never been studied, the current work sought to determine the involvement of miR-181d in neuronal apoptosis after brain I/R injury. To replicate in vivo and in vitro CI/RI, a transient middle cerebral artery occlusion (tMCAO) model in rats and an oxygen-glucose deficiency/reoxygenation (OGD/R) model in neuro 2A cells were developed. In both in vivo and in vitro stroke models, the expression of miR-181d was considerably higher. miR-181d suppression reduced apoptosis and oxidative stress in OGD/R-treated neuroblastoma cells, but miR-181d overexpression increased both. Furthermore, it was observed that miR-181d has a direct target in dedicator of cytokinesis 4 (DOCK4). The overexpression of DOCK4 partially overcame cell apoptosis and oxidative stress induced by miR-181d upregulation and OGD/R injury. Furthermore, the DOCK4 rs2074130 mutation was related to lower DOCK4 levels in ischemic stroke (IS) peripheral blood and higher susceptibility to IS. These findings suggest that downregulating miR-181d protects neurons from ischemic damage by targeting DOCK4, implying that the miR-181d/DOCK4 axis might be a novel therapeutic target for IS. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12944-023-01794-3. |
format | Online Article Text |
id | pubmed-9990210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-99902102023-03-08 Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury Li, Shengnan Chen, Shaofeng Wang, Yajun Hu, Xingjuan Wang, Ying Wu, Zhaochun Huang, Shaoting He, Jiawen Deng, Fu Zhao, Bin Ma, Guoda Li, You Lipids Health Dis Research The miRNA-181 (miR-181) family regulates neuronal persistence during cerebral ischemia/reperfusion injury (CI/RI). Since the effect of miR-181d on CI/RI has never been studied, the current work sought to determine the involvement of miR-181d in neuronal apoptosis after brain I/R injury. To replicate in vivo and in vitro CI/RI, a transient middle cerebral artery occlusion (tMCAO) model in rats and an oxygen-glucose deficiency/reoxygenation (OGD/R) model in neuro 2A cells were developed. In both in vivo and in vitro stroke models, the expression of miR-181d was considerably higher. miR-181d suppression reduced apoptosis and oxidative stress in OGD/R-treated neuroblastoma cells, but miR-181d overexpression increased both. Furthermore, it was observed that miR-181d has a direct target in dedicator of cytokinesis 4 (DOCK4). The overexpression of DOCK4 partially overcame cell apoptosis and oxidative stress induced by miR-181d upregulation and OGD/R injury. Furthermore, the DOCK4 rs2074130 mutation was related to lower DOCK4 levels in ischemic stroke (IS) peripheral blood and higher susceptibility to IS. These findings suggest that downregulating miR-181d protects neurons from ischemic damage by targeting DOCK4, implying that the miR-181d/DOCK4 axis might be a novel therapeutic target for IS. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12944-023-01794-3. BioMed Central 2023-03-07 /pmc/articles/PMC9990210/ /pubmed/36882763 http://dx.doi.org/10.1186/s12944-023-01794-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Li, Shengnan Chen, Shaofeng Wang, Yajun Hu, Xingjuan Wang, Ying Wu, Zhaochun Huang, Shaoting He, Jiawen Deng, Fu Zhao, Bin Ma, Guoda Li, You Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury |
title | Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury |
title_full | Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury |
title_fullStr | Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury |
title_full_unstemmed | Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury |
title_short | Direct targeting of DOCK4 by miRNA-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury |
title_sort | direct targeting of dock4 by mirna-181d in oxygen-glucose deprivation/reoxygenation-mediated neuronal injury |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990210/ https://www.ncbi.nlm.nih.gov/pubmed/36882763 http://dx.doi.org/10.1186/s12944-023-01794-3 |
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