miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke
Shengtao Yao,* Bo Tang,* Gang Li, Ruiming Fan, Fang Cao Department of Cerebrovascular Disease, The First Affiliated Hospital of Zunyi Medical College, Zunyi, People’s Republic of China *These authors contributed equally to this work Abstract: Ischemic stroke is one of the leading ca...
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Dove Medical Press
2016-12-01
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| Series: | Neuropsychiatric Disease and Treatment |
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| Online Access: | https://www.dovepress.com/mir-455-inhibits-neuronal-cell-death-by-targeting-traf3-in-cerebral-is-peer-reviewed-fulltext-article-NDT |
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| author | Yao ST Tang B Li G Fan RM Cao F |
| author_facet | Yao ST Tang B Li G Fan RM Cao F |
| author_sort | Yao ST |
| collection | DOAJ |
| description | Shengtao Yao,* Bo Tang,* Gang Li, Ruiming Fan, Fang Cao Department of Cerebrovascular Disease, The First Affiliated Hospital of Zunyi Medical College, Zunyi, People’s Republic of China *These authors contributed equally to this work Abstract: 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. Keywords: miR-455, neuronal cell, TRAF3, cerebral ischemic stroke, MCAO |
| format | Article |
| id | doaj-art-e7bb89acff0b448b92bb608ea23195ee |
| institution | Kabale University |
| issn | 1178-2021 |
| language | English |
| publishDate | 2016-12-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Neuropsychiatric Disease and Treatment |
| spelling | doaj-art-e7bb89acff0b448b92bb608ea23195ee2025-08-20T03:30:04ZengDove Medical PressNeuropsychiatric Disease and Treatment1178-20212016-12-01Volume 12Issue 13083309230329miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic strokeYao STTang BLi GFan RMCao F0Department of CerebrovascularShengtao Yao,* Bo Tang,* Gang Li, Ruiming Fan, Fang Cao Department of Cerebrovascular Disease, The First Affiliated Hospital of Zunyi Medical College, Zunyi, People’s Republic of China *These authors contributed equally to this work Abstract: 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. Keywords: miR-455, neuronal cell, TRAF3, cerebral ischemic stroke, MCAOhttps://www.dovepress.com/mir-455-inhibits-neuronal-cell-death-by-targeting-traf3-in-cerebral-is-peer-reviewed-fulltext-article-NDTmiR-455neuronal cellTRAF3cerebral ischemic stroke |
| spellingShingle | Yao ST Tang B Li G Fan RM Cao F miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke Neuropsychiatric Disease and Treatment miR-455 neuronal cell TRAF3 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 | miR-455 neuronal cell TRAF3 cerebral ischemic stroke |
| url | https://www.dovepress.com/mir-455-inhibits-neuronal-cell-death-by-targeting-traf3-in-cerebral-is-peer-reviewed-fulltext-article-NDT |
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