miRNA-7a-2-3p Inhibits Neuronal Apoptosis in Oxygen-Glucose Deprivation (OGD) Model
Neuronal apoptosis is a major pathological hallmark of the neonatal hypoxic-ischemic brain damage (HIBD); however, the role of miR-7a-2-3p in the regulation of HIBD remains unknown. The purpose of this study was to explore the possible roles of miR-7a-2-3p in brain injury using a hypoxia-ischemia mo...
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Frontiers Media S.A.
2019-01-01
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Series: | Frontiers in Neuroscience |
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Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2019.00016/full |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zi-Bin Zhang Zi-Bin Zhang Ya-Xin Tan Qiong Zhao Liu-Lin Xiong Jia Liu Fei-Fei Xu Yang Xu Larisa Bobrovskaya Xin-Fu Zhou Ting-Hua Wang |
spellingShingle |
Zi-Bin Zhang Zi-Bin Zhang Ya-Xin Tan Qiong Zhao Liu-Lin Xiong Jia Liu Fei-Fei Xu Yang Xu Larisa Bobrovskaya Xin-Fu Zhou Ting-Hua Wang miRNA-7a-2-3p Inhibits Neuronal Apoptosis in Oxygen-Glucose Deprivation (OGD) Model Frontiers in Neuroscience neonatal hypoxic-ischemic brain damage (HIBD) miR-7a-2-3p oxygen-glucose deprivation (OGD) neuronal apoptosis Vimentin (VIM) |
author_facet |
Zi-Bin Zhang Zi-Bin Zhang Ya-Xin Tan Qiong Zhao Liu-Lin Xiong Jia Liu Fei-Fei Xu Yang Xu Larisa Bobrovskaya Xin-Fu Zhou Ting-Hua Wang |
author_sort |
Zi-Bin Zhang |
title |
miRNA-7a-2-3p Inhibits Neuronal Apoptosis in Oxygen-Glucose Deprivation (OGD) Model |
title_short |
miRNA-7a-2-3p Inhibits Neuronal Apoptosis in Oxygen-Glucose Deprivation (OGD) Model |
title_full |
miRNA-7a-2-3p Inhibits Neuronal Apoptosis in Oxygen-Glucose Deprivation (OGD) Model |
title_fullStr |
miRNA-7a-2-3p Inhibits Neuronal Apoptosis in Oxygen-Glucose Deprivation (OGD) Model |
title_full_unstemmed |
miRNA-7a-2-3p Inhibits Neuronal Apoptosis in Oxygen-Glucose Deprivation (OGD) Model |
title_sort |
mirna-7a-2-3p inhibits neuronal apoptosis in oxygen-glucose deprivation (ogd) model |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2019-01-01 |
description |
Neuronal apoptosis is a major pathological hallmark of the neonatal hypoxic-ischemic brain damage (HIBD); however, the role of miR-7a-2-3p in the regulation of HIBD remains unknown. The purpose of this study was to explore the possible roles of miR-7a-2-3p in brain injury using a hypoxia-ischemia model in rats and oxygen-glucose deprivation (OGD) model in vitro. Firstly, we established the hypoxia-ischemia (HI) model and verified the model using Zea Longa scores and MRI in rats. Next, the changes of miR-7a-2-3p were screened in the ischemic cortex of neonatal rats by qRT-PCR at 12, 48, and 96 h after HIBD. We have found that the expression of miR-7a-2-3p in the HI rats decreased significantly, compared with the sham group (P < 0.01). Then, we established the OGD model in PC12 cells, SH-SY5Y cells and primary cortical neurons in vitro and qRT-PCR was used to confirm the changes of miR-7a-2-3p in these cells after the OGD. In order to determine the function of miR-7a-2-3p, PC12 cells, SH-SY5Y cells and rat primary cortical neurons were randomly divided into normal, OGD, mimic negative control (mimic-NC) and miR-7a-2-3p groups. Then, Tuj1+ (neuronal marker) staining, TUNEL assay (to detect apoptotic cells) and MTT assay (to investigate cell viability) were performed. We have found that the number of PC12 cells, SH-SY5Y cells and cortical neurons in the miR-7a-2-3p groups increased significantly (P < 0.01) in comparison to the OGD groups. The survival of cortical neurons in the miR-7a-2-3p group was improved markedly (P < 0.01), while the apoptosis of neurons in the miR-7a-2-3p group was significantly decreased (P < 0.01), compared with the normal group. Lastly, we investigated the target genes of miR-7a-2-3p by using the prediction databases (miRDB, TargetScan, miRWalk, and miRmap) and verified the target genes with qRT-PCR in the HI rats. Bioinformatics prediction showed that Vimentin (VIM), pleiomorphic adenoma gene 1(PLAG1), dual specificity phosphatase 10 (DUSP10), NAD(P)H dehydrogenase, quinone 1 (NQO1) and tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) might be the targets of miR-7a-2-3p and the qRT-PCR confirmed that VIM increased in the HI rats (P < 0.01). In conclusion, miR-7a-2-3p plays a crucial role in the hypoxic-ischemic injury, and is associated with regulation of VIM. |
topic |
neonatal hypoxic-ischemic brain damage (HIBD) miR-7a-2-3p oxygen-glucose deprivation (OGD) neuronal apoptosis Vimentin (VIM) |
url |
https://www.frontiersin.org/article/10.3389/fnins.2019.00016/full |
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doaj-9decfc6cf05a456f8aa34aa8eb0fa9112020-11-25T00:00:45ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-01-011310.3389/fnins.2019.00016409944miRNA-7a-2-3p Inhibits Neuronal Apoptosis in Oxygen-Glucose Deprivation (OGD) ModelZi-Bin Zhang0Zi-Bin Zhang1Ya-Xin Tan2Qiong Zhao3Liu-Lin Xiong4Jia Liu5Fei-Fei Xu6Yang Xu7Larisa Bobrovskaya8Xin-Fu Zhou9Ting-Hua Wang10Institute of Neuroscience, Kunming Medical University, Kunming, ChinaDepartment of Anesthesiology, Qilu Hospital of Shandong University, Jinan, ChinaInstitute of Neuroscience, Kunming Medical University, Kunming, ChinaDepartment of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaSchool of Pharmacy and Medical Sciences, Faculty of Health Sciences, University of South Australia, Adelaide, SA, AustraliaDepartment of Laboratory Animal Science, School of Basic Medical Sciences, Kunming Medical University, Kunming, ChinaInstitute of Neurological Diseases, Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, ChinaInstitute of Neurological Diseases, Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, ChinaSchool of Pharmacy and Medical Sciences, Faculty of Health Sciences, University of South Australia, Adelaide, SA, AustraliaSchool of Pharmacy and Medical Sciences, Faculty of Health Sciences, University of South Australia, Adelaide, SA, AustraliaInstitute of Neuroscience, Kunming Medical University, Kunming, ChinaNeuronal apoptosis is a major pathological hallmark of the neonatal hypoxic-ischemic brain damage (HIBD); however, the role of miR-7a-2-3p in the regulation of HIBD remains unknown. The purpose of this study was to explore the possible roles of miR-7a-2-3p in brain injury using a hypoxia-ischemia model in rats and oxygen-glucose deprivation (OGD) model in vitro. Firstly, we established the hypoxia-ischemia (HI) model and verified the model using Zea Longa scores and MRI in rats. Next, the changes of miR-7a-2-3p were screened in the ischemic cortex of neonatal rats by qRT-PCR at 12, 48, and 96 h after HIBD. We have found that the expression of miR-7a-2-3p in the HI rats decreased significantly, compared with the sham group (P < 0.01). Then, we established the OGD model in PC12 cells, SH-SY5Y cells and primary cortical neurons in vitro and qRT-PCR was used to confirm the changes of miR-7a-2-3p in these cells after the OGD. In order to determine the function of miR-7a-2-3p, PC12 cells, SH-SY5Y cells and rat primary cortical neurons were randomly divided into normal, OGD, mimic negative control (mimic-NC) and miR-7a-2-3p groups. Then, Tuj1+ (neuronal marker) staining, TUNEL assay (to detect apoptotic cells) and MTT assay (to investigate cell viability) were performed. We have found that the number of PC12 cells, SH-SY5Y cells and cortical neurons in the miR-7a-2-3p groups increased significantly (P < 0.01) in comparison to the OGD groups. The survival of cortical neurons in the miR-7a-2-3p group was improved markedly (P < 0.01), while the apoptosis of neurons in the miR-7a-2-3p group was significantly decreased (P < 0.01), compared with the normal group. Lastly, we investigated the target genes of miR-7a-2-3p by using the prediction databases (miRDB, TargetScan, miRWalk, and miRmap) and verified the target genes with qRT-PCR in the HI rats. Bioinformatics prediction showed that Vimentin (VIM), pleiomorphic adenoma gene 1(PLAG1), dual specificity phosphatase 10 (DUSP10), NAD(P)H dehydrogenase, quinone 1 (NQO1) and tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) might be the targets of miR-7a-2-3p and the qRT-PCR confirmed that VIM increased in the HI rats (P < 0.01). In conclusion, miR-7a-2-3p plays a crucial role in the hypoxic-ischemic injury, and is associated with regulation of VIM.https://www.frontiersin.org/article/10.3389/fnins.2019.00016/fullneonatal hypoxic-ischemic brain damage (HIBD)miR-7a-2-3poxygen-glucose deprivation (OGD)neuronal apoptosisVimentin (VIM) |