GAS5 knockdown alleviates spinal cord injury by reducing VAV1 expression via RNA binding protein CELF2

Abstract Long non-coding RNA growth arrest specific transcript 5 (GAS5) has been found to be implicated in the pathogenesis of central nervous diseases and to be a contributor to hypoxic brain injury. However, the roles and molecular mechanisms of GAS5 in spinal cord injury (SCI) have not thoroughly...

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Autores principales:	Dan Wang, Xiaoxiao Xu, Junwei Pan, Shixin Zhao, Yu Li, Zhen Wang, Jiahao Yang, Xi Zhang, Yisheng Wang, Ming Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0c235366764245929e959e8fd97c0068
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spelling	oai:doaj.org-article:0c235366764245929e959e8fd97c00682021-12-02T12:14:56ZGAS5 knockdown alleviates spinal cord injury by reducing VAV1 expression via RNA binding protein CELF210.1038/s41598-021-83145-92045-2322https://doaj.org/article/0c235366764245929e959e8fd97c00682021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83145-9https://doaj.org/toc/2045-2322Abstract Long non-coding RNA growth arrest specific transcript 5 (GAS5) has been found to be implicated in the pathogenesis of central nervous diseases and to be a contributor to hypoxic brain injury. However, the roles and molecular mechanisms of GAS5 in spinal cord injury (SCI) have not thoroughly investigated. Here, we reported that GAS5 knockdown improved rat locomotor function and alleviated pathological damage of spinal cord tissues by reducing oxidative stress, caspase-3 activity and vav guanine nucleotide exchange factor 1 (VAV1) expression in SCI rat models. GAS5 knockdown inhibited the increase of malondialdehyde (MDA) level and cell apoptotic rate induced by oxygen–glucose deprivation (OGD) and weakened the inhibitory effects of OGD on superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and cell viability in RN-Sc cells, suggesting that GAS5 loss mitigated OGD-triggered oxidative stress and cell injury in RN-Sc cells. Molecular mechanism explorations revealed that GAS5 recruited CUGBP, Elav-like family member 2 (CELF2) to the coding region of VAV1 mRNA, resulting in the increase of VAV1 mRNA stability and expression levels. VAV1 knockdown weakened OGD-induced oxidative stress and cell injury in RN-Sc cells. VAV1 loss alleviated GAS5-induced oxidative stress and cell injury in OGD-treated RN-Sc cells. As a conclusion, our findings suggested that GAS5 aggravated SCI by increasing VAV1 expression via binding with CELF2, deepening our understanding on function and molecular basis of GAS5 in SCI.Dan WangXiaoxiao XuJunwei PanShixin ZhaoYu LiZhen WangJiahao YangXi ZhangYisheng WangMing LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dan Wang Xiaoxiao Xu Junwei Pan Shixin Zhao Yu Li Zhen Wang Jiahao Yang Xi Zhang Yisheng Wang Ming Liu GAS5 knockdown alleviates spinal cord injury by reducing VAV1 expression via RNA binding protein CELF2
description	Abstract Long non-coding RNA growth arrest specific transcript 5 (GAS5) has been found to be implicated in the pathogenesis of central nervous diseases and to be a contributor to hypoxic brain injury. However, the roles and molecular mechanisms of GAS5 in spinal cord injury (SCI) have not thoroughly investigated. Here, we reported that GAS5 knockdown improved rat locomotor function and alleviated pathological damage of spinal cord tissues by reducing oxidative stress, caspase-3 activity and vav guanine nucleotide exchange factor 1 (VAV1) expression in SCI rat models. GAS5 knockdown inhibited the increase of malondialdehyde (MDA) level and cell apoptotic rate induced by oxygen–glucose deprivation (OGD) and weakened the inhibitory effects of OGD on superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and cell viability in RN-Sc cells, suggesting that GAS5 loss mitigated OGD-triggered oxidative stress and cell injury in RN-Sc cells. Molecular mechanism explorations revealed that GAS5 recruited CUGBP, Elav-like family member 2 (CELF2) to the coding region of VAV1 mRNA, resulting in the increase of VAV1 mRNA stability and expression levels. VAV1 knockdown weakened OGD-induced oxidative stress and cell injury in RN-Sc cells. VAV1 loss alleviated GAS5-induced oxidative stress and cell injury in OGD-treated RN-Sc cells. As a conclusion, our findings suggested that GAS5 aggravated SCI by increasing VAV1 expression via binding with CELF2, deepening our understanding on function and molecular basis of GAS5 in SCI.
format	article
author	Dan Wang Xiaoxiao Xu Junwei Pan Shixin Zhao Yu Li Zhen Wang Jiahao Yang Xi Zhang Yisheng Wang Ming Liu
author_facet	Dan Wang Xiaoxiao Xu Junwei Pan Shixin Zhao Yu Li Zhen Wang Jiahao Yang Xi Zhang Yisheng Wang Ming Liu
author_sort	Dan Wang
title	GAS5 knockdown alleviates spinal cord injury by reducing VAV1 expression via RNA binding protein CELF2
title_short	GAS5 knockdown alleviates spinal cord injury by reducing VAV1 expression via RNA binding protein CELF2
title_full	GAS5 knockdown alleviates spinal cord injury by reducing VAV1 expression via RNA binding protein CELF2
title_fullStr	GAS5 knockdown alleviates spinal cord injury by reducing VAV1 expression via RNA binding protein CELF2
title_full_unstemmed	GAS5 knockdown alleviates spinal cord injury by reducing VAV1 expression via RNA binding protein CELF2
title_sort	gas5 knockdown alleviates spinal cord injury by reducing vav1 expression via rna binding protein celf2
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0c235366764245929e959e8fd97c0068
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GAS5 knockdown alleviates spinal cord injury by reducing VAV1 expression via RNA binding protein CELF2

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