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Front. Neurosci. | doi: 10.3389/fnins.2019.00016

miRNA-7a-2-3p inhibits neuron apoptosis in oxygen glucose deprivation (OGD) model

  • 1Institute of Neurological Disease, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, China
  • 2Institute of Neuroscience, Kunming Medical University, China
  • 3Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China
  • 4School of Basic Medicine, Kunming Medical University, China

Neuronal apoptosis is important pathological change in neonatal hypoxic-ischemic brain damage (HIBD), while the role of miR-7a-2-3p in the regulation of HIBD remains to be unknown. The purpose of this study is to explore the mechanism of brain injury and provide theoretical basis for clinical target therapy. Firstly, we established the HI model and verified the model with Zealonga scores and MRI. Next, the changes of miR-7a-2-3p were screened in the ischemic cortex by qRT-PCR at 12h,48h and 96h after HIBD of neonatal rats. Then, we established OGD in pc12 cells, sy5y cells and neurons in vitro. Moreover, qRT-PCR was used to confirm the changes of miR-7a-2-3p in pc12 cells, sy5y cells and neurons with OGD. In order to determine the function of miR-7a-2-3p, pc12 cells, sy5y cells and neurons were used and randomly divided into normal, OGD, mimic-NC, miR-7a-2-3p group, respectively. Then, miR-7a-2-3p mimic transfection was performed and the cortical neurons with Tuj1+ staining, TUNEL staining and MTT were measured, respectively. Lastly, we predicted the target genes of miR-7a-2-3p by prediction database (miRDB, TargetScan, miRWalk and miRmap) and verified the target genes with qRT-PCR in HI rats. HI model and OGD model were successfully established. The expression of miR-7a-2-3p in HI group decreased significantly, compared with the normal group (P<0.01). In functional level, compared with OGD group, the number of pc12 cells, sy5y cells and cortical neurons in miR-7a-2-3p group increased significantly (P<0.01). Meanwhile, the activity of cortical neurons in miR-7a-2-3p group was improved markedly (P<0.01), while the number of neuron apoptosis in miR-7a-2-3p group significantly decreased (P<0.01). Lastly 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 qRT-PCR confirmed that VIM increased in HI rats (P<0.01). MiR-7a-2-3p played crucial role in hypoxic-ischemic injury, which might be associated with regulation of VIM.

Keywords: Neonatal hypoxic-ischemic brain damage (HIBD), Oxygen and Glucose Deprivation(OGD), miR-7a-2-3p, Neuronal apoptosis, Vimentin(VIM)

Received: 25 Jun 2018; Accepted: 08 Jan 2019.

Edited by:

Giuseppe Pignataro, University of Naples Federico II, Italy

Reviewed by:

Annalisa Buffo, University of Turin, Italy
Antonio Vinciguerra, University of Naples Federico II, Italy  

Copyright: © 2019 Zhang, Tan, Zhao, Xiong, Liu, Xu, Xu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Ting-Hua Wang, Institute of Neurological Disease, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China, wangtinghua@vip.163.com