Transcription Factor E2F1 Aggravates Neurological Injury in Ischemic Stroke via microRNA-122-Targeted Sprouty2

Yunxia Wu, Zhiqiang Gao, Jiang Zhang Department of Neurology, Linyi Central Hospital, Linyi, Shandong 276400, People’s Republic of ChinaCorrespondence: Jiang Zhang Department of Neurology, Linyi Central Hospital, No. 17, Jiankang Road, Yishui County, Linyi 276400, Shandong, People&rsqu...

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Autores principales:	Wu Y, Gao Z, Zhang J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	ischemic stroke e2f1 microrna-122 spry2 mapk pathway neurological injury Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/1a97495ed02640d3a6edb2f78594449a
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spelling	oai:doaj.org-article:1a97495ed02640d3a6edb2f78594449a2021-12-02T12:19:31ZTranscription Factor E2F1 Aggravates Neurological Injury in Ischemic Stroke via microRNA-122-Targeted Sprouty21178-2021https://doaj.org/article/1a97495ed02640d3a6edb2f78594449a2020-11-01T00:00:00Zhttps://www.dovepress.com/transcription-factor-e2f1-aggravates-neurological-injury-in-ischemic-s-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Yunxia Wu, Zhiqiang Gao, Jiang Zhang Department of Neurology, Linyi Central Hospital, Linyi, Shandong 276400, People’s Republic of ChinaCorrespondence: Jiang Zhang Department of Neurology, Linyi Central Hospital, No. 17, Jiankang Road, Yishui County, Linyi 276400, Shandong, People’s Republic of ChinaTel/Fax +86-0539-22260223Email Jiangzhang3241@163.comBackground: It has been documented that microRNAs (miRs) assume a pivotal role in the development of ischemic stroke (IS). However, it remains poorly identified about the role of miR-122 in IS. Herein, this study was intended to explore the mechanism of E2F1-orchestrated miR-122 in IS.Patients and Methods: E2F1, miR-122, and SPRY2 expression in serum from patients with IS and oxygen-glucose deprivation (OGD)-treated N2a cells was detected by RT-qPCR. After gain- and loss-of-function approaches in OGD-induced N2a cells, GAFP staining, flow cytometry, and Western blot analysis were adopted to assess neuronal viability, cell cycle and apoptosis, and expression of apoptosis- and autophagy-related proteins, respectively. Meanwhile, mice with IS were induced, in which E2F1, miR-122, and SPRY2 were overexpressed, followed by evaluation of neurological deficit and cerebral infarction area. The MAPK pathway activity in tissues of mice and cells was determined.Results: miR-122 was down-regulated, and E2F1 and SPRY2 were up-regulated in IS patients and OGD-induced N2a cells. E2F1 inhibited miR-122 transcription, while miR-122 targeted SPRY2. Overexpression (OE) of miR-122 or down-regulation of E2F1 or SPRY2 increased viability, but decreased apoptosis, cell cycle arrest, and autophagy in OGD-induced N2a cells. In IS mice, the neurological deficit score and cerebral infarction area were elevated, which was aggravated by up-regulating E2F1 or SPRY2 but attenuated by overexpressing miR-122. E2F1/miR-122/SPRY2 axis mediated the MAPK pathway in vivo and in vitro.Conclusion: Collectively, E2F1 reduced miR-122 transcription to up-regulate SPRY2, which inactivated MAPK pathway and promoted neurological deficit in IS.Keywords: ischemic stroke; IS, E2F1, microRNA-122, SPRY2, MAPK pathway, neurological injuryWu YGao ZZhang JDove Medical Pressarticleischemic strokee2f1microrna-122spry2mapk pathwayneurological injuryNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 16, Pp 2633-2647 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	ischemic stroke e2f1 microrna-122 spry2 mapk pathway neurological injury Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	ischemic stroke e2f1 microrna-122 spry2 mapk pathway neurological injury Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Wu Y Gao Z Zhang J Transcription Factor E2F1 Aggravates Neurological Injury in Ischemic Stroke via microRNA-122-Targeted Sprouty2
description	Yunxia Wu, Zhiqiang Gao, Jiang Zhang Department of Neurology, Linyi Central Hospital, Linyi, Shandong 276400, People’s Republic of ChinaCorrespondence: Jiang Zhang Department of Neurology, Linyi Central Hospital, No. 17, Jiankang Road, Yishui County, Linyi 276400, Shandong, People’s Republic of ChinaTel/Fax +86-0539-22260223Email Jiangzhang3241@163.comBackground: It has been documented that microRNAs (miRs) assume a pivotal role in the development of ischemic stroke (IS). However, it remains poorly identified about the role of miR-122 in IS. Herein, this study was intended to explore the mechanism of E2F1-orchestrated miR-122 in IS.Patients and Methods: E2F1, miR-122, and SPRY2 expression in serum from patients with IS and oxygen-glucose deprivation (OGD)-treated N2a cells was detected by RT-qPCR. After gain- and loss-of-function approaches in OGD-induced N2a cells, GAFP staining, flow cytometry, and Western blot analysis were adopted to assess neuronal viability, cell cycle and apoptosis, and expression of apoptosis- and autophagy-related proteins, respectively. Meanwhile, mice with IS were induced, in which E2F1, miR-122, and SPRY2 were overexpressed, followed by evaluation of neurological deficit and cerebral infarction area. The MAPK pathway activity in tissues of mice and cells was determined.Results: miR-122 was down-regulated, and E2F1 and SPRY2 were up-regulated in IS patients and OGD-induced N2a cells. E2F1 inhibited miR-122 transcription, while miR-122 targeted SPRY2. Overexpression (OE) of miR-122 or down-regulation of E2F1 or SPRY2 increased viability, but decreased apoptosis, cell cycle arrest, and autophagy in OGD-induced N2a cells. In IS mice, the neurological deficit score and cerebral infarction area were elevated, which was aggravated by up-regulating E2F1 or SPRY2 but attenuated by overexpressing miR-122. E2F1/miR-122/SPRY2 axis mediated the MAPK pathway in vivo and in vitro.Conclusion: Collectively, E2F1 reduced miR-122 transcription to up-regulate SPRY2, which inactivated MAPK pathway and promoted neurological deficit in IS.Keywords: ischemic stroke; IS, E2F1, microRNA-122, SPRY2, MAPK pathway, neurological injury
format	article
author	Wu Y Gao Z Zhang J
author_facet	Wu Y Gao Z Zhang J
author_sort	Wu Y
title	Transcription Factor E2F1 Aggravates Neurological Injury in Ischemic Stroke via microRNA-122-Targeted Sprouty2
title_short	Transcription Factor E2F1 Aggravates Neurological Injury in Ischemic Stroke via microRNA-122-Targeted Sprouty2
title_full	Transcription Factor E2F1 Aggravates Neurological Injury in Ischemic Stroke via microRNA-122-Targeted Sprouty2
title_fullStr	Transcription Factor E2F1 Aggravates Neurological Injury in Ischemic Stroke via microRNA-122-Targeted Sprouty2
title_full_unstemmed	Transcription Factor E2F1 Aggravates Neurological Injury in Ischemic Stroke via microRNA-122-Targeted Sprouty2
title_sort	transcription factor e2f1 aggravates neurological injury in ischemic stroke via microrna-122-targeted sprouty2
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/1a97495ed02640d3a6edb2f78594449a
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Transcription Factor E2F1 Aggravates Neurological Injury in Ischemic Stroke via microRNA-122-Targeted Sprouty2

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