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miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke

Ischemic stroke is one of the leading causes of brain disease, with high morbidity, disability, and mortality. MicroRNAs (miRNAs) have been identified as vital gene regulators in various types of human diseases. Accumulating evidence has suggested that aberrant expression of miRNAs play critical rol...

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Autores principales: Yao, Shengtao, Tang, Bo, Li, Gang, Fan, Ruiming, Cao, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147416/
https://www.ncbi.nlm.nih.gov/pubmed/27980410
http://dx.doi.org/10.2147/NDT.S121183
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author Yao, Shengtao
Tang, Bo
Li, Gang
Fan, Ruiming
Cao, Fang
author_facet Yao, Shengtao
Tang, Bo
Li, Gang
Fan, Ruiming
Cao, Fang
author_sort Yao, Shengtao
collection PubMed
description Ischemic stroke is one of the leading causes of brain disease, with high morbidity, disability, and mortality. MicroRNAs (miRNAs) have been identified as vital gene regulators in various types of human diseases. Accumulating evidence has suggested that aberrant expression of miRNAs play critical roles in the pathologies of ischemic stroke. Yet, the precise mechanism by which miRNAs control cerebral ischemic stroke remains unclear. In the present study, we explored whether miR-455 suppresses neuronal death by targeting TRAF3 in cerebral ischemic stroke. The expression levels of miR-455 and TRAF3 were detected by quantitative real-time polymerase chain reaction and Western blot. The role of miR-455 in cell death caused by oxygen–glucose deprivation (OGD) was assessed using Cell Counting Kit-8 (CCK-8) assay. The influence of miR-455 on infarct volume was evaluated in mouse brain after middle cerebral artery occlusion (MCAO). Bioinformatics softwares and luciferase analysis were used to find and confirm the targets of miR-455. The results showed that the expression levels of miR-455 significantly decreased in primary neuronal cells subjected to OGD and mouse brain subjected to MCAO. In addition, forced expression of miR-455 inhibited neuronal death and weakened ischemic brain infarction in focal ischemia-stroked mice. Furthermore, TRAF3 was proved to be a direct target of miR-455, and miR-455 could negatively suppress TRAF3 expression. Biological function analysis showed that TRAF3 silencing displayed the neuroprotective effect in ischemic stroke and could enhance miR-455-induced positive impact on ischemic injury both in vitro and in vivo. Taken together, miR-455 played a vital role in protecting neuronal cells from death by downregulating TRAF3 protein expression. These findings may represent a novel latent therapeutic target for cerebral ischemic stroke.
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spelling pubmed-51474162016-12-15 miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke Yao, Shengtao Tang, Bo Li, Gang Fan, Ruiming Cao, Fang Neuropsychiatr Dis Treat Original Research Ischemic stroke is one of the leading causes of brain disease, with high morbidity, disability, and mortality. MicroRNAs (miRNAs) have been identified as vital gene regulators in various types of human diseases. Accumulating evidence has suggested that aberrant expression of miRNAs play critical roles in the pathologies of ischemic stroke. Yet, the precise mechanism by which miRNAs control cerebral ischemic stroke remains unclear. In the present study, we explored whether miR-455 suppresses neuronal death by targeting TRAF3 in cerebral ischemic stroke. The expression levels of miR-455 and TRAF3 were detected by quantitative real-time polymerase chain reaction and Western blot. The role of miR-455 in cell death caused by oxygen–glucose deprivation (OGD) was assessed using Cell Counting Kit-8 (CCK-8) assay. The influence of miR-455 on infarct volume was evaluated in mouse brain after middle cerebral artery occlusion (MCAO). Bioinformatics softwares and luciferase analysis were used to find and confirm the targets of miR-455. The results showed that the expression levels of miR-455 significantly decreased in primary neuronal cells subjected to OGD and mouse brain subjected to MCAO. In addition, forced expression of miR-455 inhibited neuronal death and weakened ischemic brain infarction in focal ischemia-stroked mice. Furthermore, TRAF3 was proved to be a direct target of miR-455, and miR-455 could negatively suppress TRAF3 expression. Biological function analysis showed that TRAF3 silencing displayed the neuroprotective effect in ischemic stroke and could enhance miR-455-induced positive impact on ischemic injury both in vitro and in vivo. Taken together, miR-455 played a vital role in protecting neuronal cells from death by downregulating TRAF3 protein expression. These findings may represent a novel latent therapeutic target for cerebral ischemic stroke. Dove Medical Press 2016-12-05 /pmc/articles/PMC5147416/ /pubmed/27980410 http://dx.doi.org/10.2147/NDT.S121183 Text en © 2016 Yao et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Yao, Shengtao
Tang, Bo
Li, Gang
Fan, Ruiming
Cao, Fang
miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke
title miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke
title_full miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke
title_fullStr miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke
title_full_unstemmed miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke
title_short miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke
title_sort mir-455 inhibits neuronal cell death by targeting traf3 in cerebral ischemic stroke
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147416/
https://www.ncbi.nlm.nih.gov/pubmed/27980410
http://dx.doi.org/10.2147/NDT.S121183
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