MicroRNA-488-3p Regulates Neuronal Cell Death in Cerebral Ischemic Stroke Through Vacuolar Protein Sorting 4B (VPS4B)

Li Zhou,1 Wanxin Yang,1 Enping Yao,1 Haiyan Li,2 Jihui Wang,2 Kun Wang,3 Xiaohua Zhong,1 Zhongxing Peng,4 Xuming Huang1 1Department of Rehabilitation, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, People’s Republic of China; 2Department of Neurolog...

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Autores principales:	Zhou L, Yang W, Yao E, Li H, Wang J, Wang K, Zhong X, Peng Z, Huang X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	mir-488-3p vps4b ischemia/reperfusion (i/r) ischemic stroke Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/294dbb7a79c846eabb45a90ac20321bf
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spelling	oai:doaj.org-article:294dbb7a79c846eabb45a90ac20321bf2021-12-02T10:35:13ZMicroRNA-488-3p Regulates Neuronal Cell Death in Cerebral Ischemic Stroke Through Vacuolar Protein Sorting 4B (VPS4B)1178-2021https://doaj.org/article/294dbb7a79c846eabb45a90ac20321bf2021-01-01T00:00:00Zhttps://www.dovepress.com/microrna-488-3p-regulates-neuronal-cell-death-in-cerebral-ischemic-str-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Li Zhou,1 Wanxin Yang,1 Enping Yao,1 Haiyan Li,2 Jihui Wang,2 Kun Wang,3 Xiaohua Zhong,1 Zhongxing Peng,4 Xuming Huang1 1Department of Rehabilitation, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, People’s Republic of China; 2Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, People’s Republic of China; 3School of Health Science, Guangdong Pharmaceutical University, Guangzhou 510310, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, People’s Republic of ChinaCorrespondence: Xuming HuangDepartment of Rehabilitation, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, People’s Republic of ChinaTel +86-20-82804660Email zr0370@163.comZhongxing PengDepartment of Neurology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, People’s Republic of ChinaEmail pliunblgeve68@163.comBackground: Ischemic stroke, which often occurs with high morbidity, disability, and mortality, is a main cause of brain disease. In various types of human diseases, it is found that microRNAs (miRNAs) are considered as gene regulators. Increasing studies have proved that fluctuation of miRNAs, in the pathologies of ischemic stroke, plays a vital role. However, the accurate regulatory mechanism of cerebral ischemic stroke by miRNAs is still unclear. In this research, we investigated the inhibition mechanism of miR-488-3p on neuronal death through targeting vacuolar protein sorting 4B (VPS4B) in cerebral ischemia/reperfusion (I/R) injury.Methods: Western blot and qRT-PCR were utilized to detect the miR-488-3p level and VPS4B expression. The cell counting kit-8 (CCK-8) assay was utilized to measure the function of miR-488-3p in cell death induced by oxygen glucose deprivation/reoxygenation (OGD/R). After middle cerebral artery occlusion/reperfusion (MCAO/R), the impact of miR-488-3p on infarct volume in mouse brain was assessed. The targets of miR-488-3p were confirmed by luciferase analysis and bioinformatics software.Results: The miR-488-3p level remarkably reduced in primary neuronal cells administrated with OGD/R. Similarly, it also decreased in the mouse brain administrated with MCAO/R. Additionally, the up-regulation of miR-488-3p expression suppressed the death of neuronal cells and restrained ischemic brain infarction in ischemia-stroked mice. Besides, the results showed that VPS4B, which could be inhibited by miR-488-3p, was a direct target of miR-488-3p. This research revealed that the inhibition of VPS4B protected the neuronal cells in ischemic stroke both in vitro as well as in vivo. Meanwhile, this inhibition strengthened positive impact generated by miR-488-3p on ischemic injury.Conclusion: Overall, miR-488-3p played a critical role on neuroprotective function via reducing VPS4B protein level. These results performed a new underlying curative target for the treatment of cerebral ischemic stroke.Keywords: miR-488-3p, VPS4B, ischemia/reperfusion, I/R, ischemic strokeZhou LYang WYao ELi HWang JWang KZhong XPeng ZHuang XDove Medical Pressarticlemir-488-3pvps4bischemia/reperfusion (i/r)ischemic strokeNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 41-55 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mir-488-3p vps4b ischemia/reperfusion (i/r) ischemic stroke Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	mir-488-3p vps4b ischemia/reperfusion (i/r) ischemic stroke Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Zhou L Yang W Yao E Li H Wang J Wang K Zhong X Peng Z Huang X MicroRNA-488-3p Regulates Neuronal Cell Death in Cerebral Ischemic Stroke Through Vacuolar Protein Sorting 4B (VPS4B)
description	Li Zhou,1 Wanxin Yang,1 Enping Yao,1 Haiyan Li,2 Jihui Wang,2 Kun Wang,3 Xiaohua Zhong,1 Zhongxing Peng,4 Xuming Huang1 1Department of Rehabilitation, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, People’s Republic of China; 2Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, People’s Republic of China; 3School of Health Science, Guangdong Pharmaceutical University, Guangzhou 510310, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, People’s Republic of ChinaCorrespondence: Xuming HuangDepartment of Rehabilitation, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, People’s Republic of ChinaTel +86-20-82804660Email zr0370@163.comZhongxing PengDepartment of Neurology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, People’s Republic of ChinaEmail pliunblgeve68@163.comBackground: Ischemic stroke, which often occurs with high morbidity, disability, and mortality, is a main cause of brain disease. In various types of human diseases, it is found that microRNAs (miRNAs) are considered as gene regulators. Increasing studies have proved that fluctuation of miRNAs, in the pathologies of ischemic stroke, plays a vital role. However, the accurate regulatory mechanism of cerebral ischemic stroke by miRNAs is still unclear. In this research, we investigated the inhibition mechanism of miR-488-3p on neuronal death through targeting vacuolar protein sorting 4B (VPS4B) in cerebral ischemia/reperfusion (I/R) injury.Methods: Western blot and qRT-PCR were utilized to detect the miR-488-3p level and VPS4B expression. The cell counting kit-8 (CCK-8) assay was utilized to measure the function of miR-488-3p in cell death induced by oxygen glucose deprivation/reoxygenation (OGD/R). After middle cerebral artery occlusion/reperfusion (MCAO/R), the impact of miR-488-3p on infarct volume in mouse brain was assessed. The targets of miR-488-3p were confirmed by luciferase analysis and bioinformatics software.Results: The miR-488-3p level remarkably reduced in primary neuronal cells administrated with OGD/R. Similarly, it also decreased in the mouse brain administrated with MCAO/R. Additionally, the up-regulation of miR-488-3p expression suppressed the death of neuronal cells and restrained ischemic brain infarction in ischemia-stroked mice. Besides, the results showed that VPS4B, which could be inhibited by miR-488-3p, was a direct target of miR-488-3p. This research revealed that the inhibition of VPS4B protected the neuronal cells in ischemic stroke both in vitro as well as in vivo. Meanwhile, this inhibition strengthened positive impact generated by miR-488-3p on ischemic injury.Conclusion: Overall, miR-488-3p played a critical role on neuroprotective function via reducing VPS4B protein level. These results performed a new underlying curative target for the treatment of cerebral ischemic stroke.Keywords: miR-488-3p, VPS4B, ischemia/reperfusion, I/R, ischemic stroke
format	article
author	Zhou L Yang W Yao E Li H Wang J Wang K Zhong X Peng Z Huang X
author_facet	Zhou L Yang W Yao E Li H Wang J Wang K Zhong X Peng Z Huang X
author_sort	Zhou L
title	MicroRNA-488-3p Regulates Neuronal Cell Death in Cerebral Ischemic Stroke Through Vacuolar Protein Sorting 4B (VPS4B)
title_short	MicroRNA-488-3p Regulates Neuronal Cell Death in Cerebral Ischemic Stroke Through Vacuolar Protein Sorting 4B (VPS4B)
title_full	MicroRNA-488-3p Regulates Neuronal Cell Death in Cerebral Ischemic Stroke Through Vacuolar Protein Sorting 4B (VPS4B)
title_fullStr	MicroRNA-488-3p Regulates Neuronal Cell Death in Cerebral Ischemic Stroke Through Vacuolar Protein Sorting 4B (VPS4B)
title_full_unstemmed	MicroRNA-488-3p Regulates Neuronal Cell Death in Cerebral Ischemic Stroke Through Vacuolar Protein Sorting 4B (VPS4B)
title_sort	microrna-488-3p regulates neuronal cell death in cerebral ischemic stroke through vacuolar protein sorting 4b (vps4b)
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/294dbb7a79c846eabb45a90ac20321bf
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MicroRNA-488-3p Regulates Neuronal Cell Death in Cerebral Ischemic Stroke Through Vacuolar Protein Sorting 4B (VPS4B)

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