YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA

YTH Domain Containing 1 (YTHDC1) is one of the m(6)A readers that is essential for oocyte development and tumor progression. The role of YTHDC1 in neuronal survival and ischemic stroke is unknown. Here, we found that YTHDC1 was unregulated in the early phase of ischemic stroke. Knockdown of YTHDC1 e...

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Autores principales: Zhang, Zhaolong, Wang, Qiuhan, Zhao, Xiaolong, Shao, Liming, Liu, Guoping, Zheng, Xuan, Xie, Lingling, Zhang, Yan, Sun, Chengjian, Xu, Rui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666223/
https://www.ncbi.nlm.nih.gov/pubmed/33188203
http://dx.doi.org/10.1038/s41419-020-03186-2
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author Zhang, Zhaolong
Wang, Qiuhan
Zhao, Xiaolong
Shao, Liming
Liu, Guoping
Zheng, Xuan
Xie, Lingling
Zhang, Yan
Sun, Chengjian
Xu, Rui
author_facet Zhang, Zhaolong
Wang, Qiuhan
Zhao, Xiaolong
Shao, Liming
Liu, Guoping
Zheng, Xuan
Xie, Lingling
Zhang, Yan
Sun, Chengjian
Xu, Rui
author_sort Zhang, Zhaolong
collection PubMed
description YTH Domain Containing 1 (YTHDC1) is one of the m(6)A readers that is essential for oocyte development and tumor progression. The role of YTHDC1 in neuronal survival and ischemic stroke is unknown. Here, we found that YTHDC1 was unregulated in the early phase of ischemic stroke. Knockdown of YTHDC1 exacerbated ischemic brain injury and overexpression of YTHDC1 protected rats against brain injury. Mechanistically, YTHDC1 promoted PTEN mRNA degradation to increase Akt phosphorylation, thus facilitating neuronal survival in particular after ischemia. These data identify YTHDC1 as a novel regulator of neuronal survival and modulating m(6)A reader YTHDC1 may provide a potential therapeutic target for ischemic stroke.
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spelling pubmed-76662232020-11-17 YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA Zhang, Zhaolong Wang, Qiuhan Zhao, Xiaolong Shao, Liming Liu, Guoping Zheng, Xuan Xie, Lingling Zhang, Yan Sun, Chengjian Xu, Rui Cell Death Dis Article YTH Domain Containing 1 (YTHDC1) is one of the m(6)A readers that is essential for oocyte development and tumor progression. The role of YTHDC1 in neuronal survival and ischemic stroke is unknown. Here, we found that YTHDC1 was unregulated in the early phase of ischemic stroke. Knockdown of YTHDC1 exacerbated ischemic brain injury and overexpression of YTHDC1 protected rats against brain injury. Mechanistically, YTHDC1 promoted PTEN mRNA degradation to increase Akt phosphorylation, thus facilitating neuronal survival in particular after ischemia. These data identify YTHDC1 as a novel regulator of neuronal survival and modulating m(6)A reader YTHDC1 may provide a potential therapeutic target for ischemic stroke. Nature Publishing Group UK 2020-11-13 /pmc/articles/PMC7666223/ /pubmed/33188203 http://dx.doi.org/10.1038/s41419-020-03186-2 Text en © The Author(s) 2020 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Zhaolong
Wang, Qiuhan
Zhao, Xiaolong
Shao, Liming
Liu, Guoping
Zheng, Xuan
Xie, Lingling
Zhang, Yan
Sun, Chengjian
Xu, Rui
YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA
title YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA
title_full YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA
title_fullStr YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA
title_full_unstemmed YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA
title_short YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA
title_sort ythdc1 mitigates ischemic stroke by promoting akt phosphorylation through destabilizing pten mrna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666223/
https://www.ncbi.nlm.nih.gov/pubmed/33188203
http://dx.doi.org/10.1038/s41419-020-03186-2
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