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LncRNA Taurine Up-Regulated 1 plays a proapoptotic role by regulating nuclear-cytoplasmic shuttle of HuR under the condition of neuronal ischemia
The study aimed to identify TUG1 as an essential regulator of apoptosis in HT22 (mouse hippocampal neuronal cells) by direct interaction with the RNA-binding protein HuR. In order to study the role of TUG1 in the context of ischemia, we used mouse hippocampal neuronal cells treated with oxyglucose d...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9648984/ https://www.ncbi.nlm.nih.gov/pubmed/36367790 http://dx.doi.org/10.1097/WNR.0000000000001848 |
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author | Shi, Xiaocheng Wei, Wei Zou, Yichun Dong, Lixin Wu, Hengping Jiang, Jiazhi Li, Xiang Chen, Jincao |
author_facet | Shi, Xiaocheng Wei, Wei Zou, Yichun Dong, Lixin Wu, Hengping Jiang, Jiazhi Li, Xiang Chen, Jincao |
author_sort | Shi, Xiaocheng |
collection | PubMed |
description | The study aimed to identify TUG1 as an essential regulator of apoptosis in HT22 (mouse hippocampal neuronal cells) by direct interaction with the RNA-binding protein HuR. In order to study the role of TUG1 in the context of ischemia, we used mouse hippocampal neuronal cells treated with oxyglucose deprivation to establish an in-vitro ischemia model. A bioinformatic analysis and formaldehyde RNA immunoprecipitation (fRIP) were used to investigate the biological functions. A Western blot assay and reverse transcription polymerase chain reaction were used to explore the expression of the molecules involved. A cell proliferation and cytotoxicity assay was performed to detect neuronal apoptosis. TUG1 exhibits a localization-specific expression pattern in HT22 cells under OGD treatment. The bioinformatics analysis showed a strong correlation between the TUG1 and HuR as predicted, and this interaction was subsequently confirmed by fRIP-qPCR. We found that HuR was translocated from the nucleus to the cytoplasm after ischemia treatment and subsequently targeted and stabilized COX-2 mRNA, which led to elevated COX-2 mRNA levels and apoptosis of the HT22 cells. Furthermore, nuclear-specific disruption of TUG1 prevented the translocation of HuR to the cytoplasm and decreased COX-2 mRNA expression, resulting in increased cell viability and partially reversed apoptosis. In conclusion, it was demonstrated that TUG1 accelerates the process of apoptosis by promoting the transfer of HuR to the cytoplasm and stabilizing COX-2 mRNA. These results provide useful information concerning a therapeutic target for ischemic stroke. |
format | Online Article Text |
id | pubmed-9648984 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-96489842022-11-14 LncRNA Taurine Up-Regulated 1 plays a proapoptotic role by regulating nuclear-cytoplasmic shuttle of HuR under the condition of neuronal ischemia Shi, Xiaocheng Wei, Wei Zou, Yichun Dong, Lixin Wu, Hengping Jiang, Jiazhi Li, Xiang Chen, Jincao Neuroreport Cellular, Molecular and Developmental Neuroscience The study aimed to identify TUG1 as an essential regulator of apoptosis in HT22 (mouse hippocampal neuronal cells) by direct interaction with the RNA-binding protein HuR. In order to study the role of TUG1 in the context of ischemia, we used mouse hippocampal neuronal cells treated with oxyglucose deprivation to establish an in-vitro ischemia model. A bioinformatic analysis and formaldehyde RNA immunoprecipitation (fRIP) were used to investigate the biological functions. A Western blot assay and reverse transcription polymerase chain reaction were used to explore the expression of the molecules involved. A cell proliferation and cytotoxicity assay was performed to detect neuronal apoptosis. TUG1 exhibits a localization-specific expression pattern in HT22 cells under OGD treatment. The bioinformatics analysis showed a strong correlation between the TUG1 and HuR as predicted, and this interaction was subsequently confirmed by fRIP-qPCR. We found that HuR was translocated from the nucleus to the cytoplasm after ischemia treatment and subsequently targeted and stabilized COX-2 mRNA, which led to elevated COX-2 mRNA levels and apoptosis of the HT22 cells. Furthermore, nuclear-specific disruption of TUG1 prevented the translocation of HuR to the cytoplasm and decreased COX-2 mRNA expression, resulting in increased cell viability and partially reversed apoptosis. In conclusion, it was demonstrated that TUG1 accelerates the process of apoptosis by promoting the transfer of HuR to the cytoplasm and stabilizing COX-2 mRNA. These results provide useful information concerning a therapeutic target for ischemic stroke. Lippincott Williams & Wilkins 2022-10-27 2022-12-14 /pmc/articles/PMC9648984/ /pubmed/36367790 http://dx.doi.org/10.1097/WNR.0000000000001848 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Cellular, Molecular and Developmental Neuroscience Shi, Xiaocheng Wei, Wei Zou, Yichun Dong, Lixin Wu, Hengping Jiang, Jiazhi Li, Xiang Chen, Jincao LncRNA Taurine Up-Regulated 1 plays a proapoptotic role by regulating nuclear-cytoplasmic shuttle of HuR under the condition of neuronal ischemia |
title | LncRNA Taurine Up-Regulated 1 plays a proapoptotic role by regulating nuclear-cytoplasmic shuttle of HuR under the condition of neuronal ischemia |
title_full | LncRNA Taurine Up-Regulated 1 plays a proapoptotic role by regulating nuclear-cytoplasmic shuttle of HuR under the condition of neuronal ischemia |
title_fullStr | LncRNA Taurine Up-Regulated 1 plays a proapoptotic role by regulating nuclear-cytoplasmic shuttle of HuR under the condition of neuronal ischemia |
title_full_unstemmed | LncRNA Taurine Up-Regulated 1 plays a proapoptotic role by regulating nuclear-cytoplasmic shuttle of HuR under the condition of neuronal ischemia |
title_short | LncRNA Taurine Up-Regulated 1 plays a proapoptotic role by regulating nuclear-cytoplasmic shuttle of HuR under the condition of neuronal ischemia |
title_sort | lncrna taurine up-regulated 1 plays a proapoptotic role by regulating nuclear-cytoplasmic shuttle of hur under the condition of neuronal ischemia |
topic | Cellular, Molecular and Developmental Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9648984/ https://www.ncbi.nlm.nih.gov/pubmed/36367790 http://dx.doi.org/10.1097/WNR.0000000000001848 |
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