MiR-101 Protects Against the Cerebral I/R Injury Through Regulating JAK2/STAT3 Signaling Pathway

Xiaowang Guo,1 Xiaoyan Shen,2 Zhijun Yong3 1Department Emergency Medicine, Shaanxi Provincial People’s Hospital, Xi’an City, Shaanxi Province, 710068, People’s Republic of China; 2Department of Neurology Medicine, The Fourth People’s Hospital of Shaanxi, Xi’an City, Shaanxi Province, 710000, People’...

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Autores principales:	Guo X, Shen X, Yong Z
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	ischemic stroke mir-101 jak2/stat3 signaling Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/d2a087c663984772a568402d286d4c65
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spelling	oai:doaj.org-article:d2a087c663984772a568402d286d4c652021-12-02T15:11:24ZMiR-101 Protects Against the Cerebral I/R Injury Through Regulating JAK2/STAT3 Signaling Pathway1178-2021https://doaj.org/article/d2a087c663984772a568402d286d4c652021-08-01T00:00:00Zhttps://www.dovepress.com/mir-101-protects-against-the-cerebral-ir-injury-through-regulating-jak-peer-reviewed-fulltext-article-NDThttps://doaj.org/toc/1178-2021Xiaowang Guo,1 Xiaoyan Shen,2 Zhijun Yong3 1Department Emergency Medicine, Shaanxi Provincial People’s Hospital, Xi’an City, Shaanxi Province, 710068, People’s Republic of China; 2Department of Neurology Medicine, The Fourth People’s Hospital of Shaanxi, Xi’an City, Shaanxi Province, 710000, People’s Republic of China; 3Department of Rehabilitation Medicine, Shaanxi Provincial People’s Hospital, Xi’an City, Shaanxi Province, 710068, People’s Republic of ChinaCorrespondence: Zhijun YongDepartment of Rehabilitation Medicine, Shaanxi Provincial People’s Hospital, No. 256 Youyi West Road, Xi’an City, Shaanxi Province, 710068, People’s Republic of ChinaEmail zhijunyongmedicine@163.comBackground: Ischemic stroke is a devastating disease with very limited therapeutics. Although miR-101 has been reported to play crucial roles in various human diseases, its role in ischemic stroke remains unclear.Methods: Ischemia-reperfusion (I/R) injury neuronal cells and rat model with I/R injury were constructed. Viability and apoptosis of I/R model cells with miR-101 overexpression or downregulation were evaluated. Potential targets of miR-101 were predicted using miRNA database microRNA.org and confirmed using luciferase reporter assays. Meanwhile, JAK2 and p-STAT3 protein levels were evaluated by Western blot. In addition, rescue experiments (silencing of JAK2) were applied to determine the role of miR-101 in cerebral I/R injury.Results: MiR-101 was significantly downregulated in OGD/R-induced neuronal cells and brain tissues with I/R injury. MiR-101 overexpression (miR-101 mimics) significantly promoted viability and inhibited apoptosis of OGD/R-induced neuronal cells in vitro and efficiently protected rats from ischemic brain injury in vivo. By contrast, miR-101 inhibitor exacerbated growth defect, apoptosis, and ischemic brain injury. Luciferase reporter assay indicated that JAK2 was a direct target of mIR-101, and JAK2 silencing effectively reversed the miR-101 inhibitor-induced neuronal cell apoptosis in vitro and reduced cerebral infarction volume in vivo.Conclusion: Our study demonstrated that miR-101 efficiently protected neuronal cells from apoptosis and ischemic brain injury through regulating the JAK2/STAT3 signaling pathway, suggesting that miR-101 might be a potential target for treatment of ischemic stroke.Keywords: ischemic stroke, miR-101, JAK2/STAT3 signalingGuo XShen XYong ZDove Medical Pressarticleischemic strokemir-101jak2/stat3 signalingNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 2791-2802 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ischemic stroke mir-101 jak2/stat3 signaling Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	ischemic stroke mir-101 jak2/stat3 signaling Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Guo X Shen X Yong Z MiR-101 Protects Against the Cerebral I/R Injury Through Regulating JAK2/STAT3 Signaling Pathway
description	Xiaowang Guo,1 Xiaoyan Shen,2 Zhijun Yong3 1Department Emergency Medicine, Shaanxi Provincial People’s Hospital, Xi’an City, Shaanxi Province, 710068, People’s Republic of China; 2Department of Neurology Medicine, The Fourth People’s Hospital of Shaanxi, Xi’an City, Shaanxi Province, 710000, People’s Republic of China; 3Department of Rehabilitation Medicine, Shaanxi Provincial People’s Hospital, Xi’an City, Shaanxi Province, 710068, People’s Republic of ChinaCorrespondence: Zhijun YongDepartment of Rehabilitation Medicine, Shaanxi Provincial People’s Hospital, No. 256 Youyi West Road, Xi’an City, Shaanxi Province, 710068, People’s Republic of ChinaEmail zhijunyongmedicine@163.comBackground: Ischemic stroke is a devastating disease with very limited therapeutics. Although miR-101 has been reported to play crucial roles in various human diseases, its role in ischemic stroke remains unclear.Methods: Ischemia-reperfusion (I/R) injury neuronal cells and rat model with I/R injury were constructed. Viability and apoptosis of I/R model cells with miR-101 overexpression or downregulation were evaluated. Potential targets of miR-101 were predicted using miRNA database microRNA.org and confirmed using luciferase reporter assays. Meanwhile, JAK2 and p-STAT3 protein levels were evaluated by Western blot. In addition, rescue experiments (silencing of JAK2) were applied to determine the role of miR-101 in cerebral I/R injury.Results: MiR-101 was significantly downregulated in OGD/R-induced neuronal cells and brain tissues with I/R injury. MiR-101 overexpression (miR-101 mimics) significantly promoted viability and inhibited apoptosis of OGD/R-induced neuronal cells in vitro and efficiently protected rats from ischemic brain injury in vivo. By contrast, miR-101 inhibitor exacerbated growth defect, apoptosis, and ischemic brain injury. Luciferase reporter assay indicated that JAK2 was a direct target of mIR-101, and JAK2 silencing effectively reversed the miR-101 inhibitor-induced neuronal cell apoptosis in vitro and reduced cerebral infarction volume in vivo.Conclusion: Our study demonstrated that miR-101 efficiently protected neuronal cells from apoptosis and ischemic brain injury through regulating the JAK2/STAT3 signaling pathway, suggesting that miR-101 might be a potential target for treatment of ischemic stroke.Keywords: ischemic stroke, miR-101, JAK2/STAT3 signaling
format	article
author	Guo X Shen X Yong Z
author_facet	Guo X Shen X Yong Z
author_sort	Guo X
title	MiR-101 Protects Against the Cerebral I/R Injury Through Regulating JAK2/STAT3 Signaling Pathway
title_short	MiR-101 Protects Against the Cerebral I/R Injury Through Regulating JAK2/STAT3 Signaling Pathway
title_full	MiR-101 Protects Against the Cerebral I/R Injury Through Regulating JAK2/STAT3 Signaling Pathway
title_fullStr	MiR-101 Protects Against the Cerebral I/R Injury Through Regulating JAK2/STAT3 Signaling Pathway
title_full_unstemmed	MiR-101 Protects Against the Cerebral I/R Injury Through Regulating JAK2/STAT3 Signaling Pathway
title_sort	mir-101 protects against the cerebral i/r injury through regulating jak2/stat3 signaling pathway
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/d2a087c663984772a568402d286d4c65
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MiR-101 Protects Against the Cerebral I/R Injury Through Regulating JAK2/STAT3 Signaling Pathway

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