NR4A2 Exacerbates Cerebral Ischemic Brain Injury via Modulating microRNA-652/Mul1 Pathway

Qiandong Liu, Qinglin Dong Department of Emergency, People’s Hospital of Rizhao, Rizhao 276800, Shandong, People’s Republic of ChinaCorrespondence: Qinglin DongDepartment of Emergency, People’s Hospital of Rizhao, No. 126, Tai’an Road, Donggang District, Rizha...

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Autores principales:	Liu Q, Dong Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	ischemic brain injury nr4a2 microrna-652 mul1 transient global cerebral ischemia Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/2745a9c463554b78a140a58a37885104
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spelling	oai:doaj.org-article:2745a9c463554b78a140a58a378851042021-12-02T10:37:34ZNR4A2 Exacerbates Cerebral Ischemic Brain Injury via Modulating microRNA-652/Mul1 Pathway1178-2021https://doaj.org/article/2745a9c463554b78a140a58a378851042020-10-01T00:00:00Zhttps://www.dovepress.com/nr4a2-exacerbates-cerebral-ischemic-brain-injury-via-modulating-micror-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Qiandong Liu, Qinglin Dong Department of Emergency, People’s Hospital of Rizhao, Rizhao 276800, Shandong, People’s Republic of ChinaCorrespondence: Qinglin DongDepartment of Emergency, People’s Hospital of Rizhao, No. 126, Tai’an Road, Donggang District, Rizhao 276800, Shandong, People’s Republic of ChinaTel/Fax +86-0633-3365983Email Qinlind0321@163.comBackground: Nuclear receptor subfamily group A member 2 (NR4A2), a transcription factor, was suggested to be involved in the pathogenesis of ischemic stroke. Nevertheless, the specific role of NR4A2 in ischemic brain injury has yet to be elucidated. Our aim was to probe the mechanisms behind the repression of microRNA (miRNA) expression resulting from NR4A2 regulation in ischemic brain injury.Methods: A rat model with transient global cerebral ischemia (tGCI) was established, followed by HE staining and immunohistochemistry for verification. Subsequently, NR4A2 expression in rat brain tissues was detected by RT-qPCR, Western blot and immunohistochemistry. Then, PC12 cells were treated with NR4A2 alteration and subjected to oxygen-glucose deprivation (OGD) for cerebral ischemia simulation. Cell viability, apoptosis and cycle distribution were detected by CCK-8 and flow cytometry, respectively. miR-652 expression in rat brain tissues and cells was then detected by RT-qPCR, and then the targeting mRNAs of miR-652 were predicted through bioinformatic websites. Finally, the effect of miR-652 and mitochondrial E3 ubiquitin ligase 1 (Mul1) on the PC12 cell activity after OGD treatment was verified by rescue experiments.Results: NR4A2 and Mul1 were expressed highly in brain tissues of rats with tGCI, while miR-652 was expressed poorly. NR4A2 inhibited the expression of miR-652 by transcription, thus blocking the inhibition of miR-652 on Mul1 to repress PC12 cell activity and promote apoptosis and G0/G1 cell cycle arrest.Conclusion: The transcription factor NR4A2 mediates the expression of Mul1 through transcriptional repression of miR-652, thus promoting ischemic brain injury.Keywords: ischemic brain injury, NR4A2, microRNA-652, Mul1, transient global cerebral ischemiaLiu QDong QDove Medical Pressarticleischemic brain injurynr4a2microrna-652mul1transient global cerebral ischemiaNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 16, Pp 2285-2296 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	ischemic brain injury nr4a2 microrna-652 mul1 transient global cerebral ischemia Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	ischemic brain injury nr4a2 microrna-652 mul1 transient global cerebral ischemia Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Liu Q Dong Q NR4A2 Exacerbates Cerebral Ischemic Brain Injury via Modulating microRNA-652/Mul1 Pathway
description	Qiandong Liu, Qinglin Dong Department of Emergency, People’s Hospital of Rizhao, Rizhao 276800, Shandong, People’s Republic of ChinaCorrespondence: Qinglin DongDepartment of Emergency, People’s Hospital of Rizhao, No. 126, Tai’an Road, Donggang District, Rizhao 276800, Shandong, People’s Republic of ChinaTel/Fax +86-0633-3365983Email Qinlind0321@163.comBackground: Nuclear receptor subfamily group A member 2 (NR4A2), a transcription factor, was suggested to be involved in the pathogenesis of ischemic stroke. Nevertheless, the specific role of NR4A2 in ischemic brain injury has yet to be elucidated. Our aim was to probe the mechanisms behind the repression of microRNA (miRNA) expression resulting from NR4A2 regulation in ischemic brain injury.Methods: A rat model with transient global cerebral ischemia (tGCI) was established, followed by HE staining and immunohistochemistry for verification. Subsequently, NR4A2 expression in rat brain tissues was detected by RT-qPCR, Western blot and immunohistochemistry. Then, PC12 cells were treated with NR4A2 alteration and subjected to oxygen-glucose deprivation (OGD) for cerebral ischemia simulation. Cell viability, apoptosis and cycle distribution were detected by CCK-8 and flow cytometry, respectively. miR-652 expression in rat brain tissues and cells was then detected by RT-qPCR, and then the targeting mRNAs of miR-652 were predicted through bioinformatic websites. Finally, the effect of miR-652 and mitochondrial E3 ubiquitin ligase 1 (Mul1) on the PC12 cell activity after OGD treatment was verified by rescue experiments.Results: NR4A2 and Mul1 were expressed highly in brain tissues of rats with tGCI, while miR-652 was expressed poorly. NR4A2 inhibited the expression of miR-652 by transcription, thus blocking the inhibition of miR-652 on Mul1 to repress PC12 cell activity and promote apoptosis and G0/G1 cell cycle arrest.Conclusion: The transcription factor NR4A2 mediates the expression of Mul1 through transcriptional repression of miR-652, thus promoting ischemic brain injury.Keywords: ischemic brain injury, NR4A2, microRNA-652, Mul1, transient global cerebral ischemia
format	article
author	Liu Q Dong Q
author_facet	Liu Q Dong Q
author_sort	Liu Q
title	NR4A2 Exacerbates Cerebral Ischemic Brain Injury via Modulating microRNA-652/Mul1 Pathway
title_short	NR4A2 Exacerbates Cerebral Ischemic Brain Injury via Modulating microRNA-652/Mul1 Pathway
title_full	NR4A2 Exacerbates Cerebral Ischemic Brain Injury via Modulating microRNA-652/Mul1 Pathway
title_fullStr	NR4A2 Exacerbates Cerebral Ischemic Brain Injury via Modulating microRNA-652/Mul1 Pathway
title_full_unstemmed	NR4A2 Exacerbates Cerebral Ischemic Brain Injury via Modulating microRNA-652/Mul1 Pathway
title_sort	nr4a2 exacerbates cerebral ischemic brain injury via modulating microrna-652/mul1 pathway
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/2745a9c463554b78a140a58a37885104
work_keys_str_mv	AT liuq nr4a2exacerbatescerebralischemicbraininjuryviamodulatingmicrorna652mul1pathway AT dongq nr4a2exacerbatescerebralischemicbraininjuryviamodulatingmicrorna652mul1pathway
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NR4A2 Exacerbates Cerebral Ischemic Brain Injury via Modulating microRNA-652/Mul1 Pathway

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