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Int. J. Mol. Sci. 2016, 17(9), 1427; doi:10.3390/ijms17091427

MicroRNA-378 Alleviates Cerebral Ischemic Injury by Negatively Regulating Apoptosis Executioner Caspase-3

1
Department of Human Anatomy, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
2
Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China
*
Author to whom correspondence should be addressed.
Academic Editor: Martin Pichler
Received: 22 July 2016 / Revised: 14 August 2016 / Accepted: 19 August 2016 / Published: 2 September 2016
(This article belongs to the Collection Regulation by Non-Coding RNAs)
View Full-Text   |   Download PDF [8154 KB, uploaded 2 September 2016]   |  

Abstract

miRNAs have been linked to many human diseases, including ischemic stroke, and are being pursued as clinical diagnostics and therapeutic targets. Among the aberrantly expressed miRNAs in our previous report using large-scale microarray screening, the downregulation of miR-378 in the peri-infarct region of middle cerebral artery occluded (MCAO) mice can be reversed by hypoxic preconditioning (HPC). In this study, the role of miR-378 in the ischemic injury was further explored. We found that miR-378 levels significantly decreased in N2A cells following oxygen-glucose deprivation (OGD) treatment. Overexpression of miR-378 significantly enhanced cell viability, decreased TUNEL-positive cells and the immunoreactivity of cleaved-caspase-3. Conversely, downregulation of miR-378 aggravated OGD-induced apoptosis and ischemic injury. By using bioinformatic algorithms, we discovered that miR-378 may directly bind to the predicted 3′-untranslated region (UTR) of Caspase-3 gene. The protein level of caspase-3 increased significantly upon OGD treatment, and can be downregulated by pri-miR-378 transfection. The luciferase reporter assay confirmed the binding of miR-378 to the 3′-UTR of Caspase-3 mRNA and repressed its translation. In addition, miR-378 agomir decreased cleaved-caspase-3 ratio, reduced infarct volume and neural cell death induced by MCAO. Furthermore, caspase-3 knockdown could reverse anti-miR-378 mediated neuronal injury. Taken together, our data demonstrated that miR-378 attenuated ischemic injury by negatively regulating the apoptosis executioner, caspase-3, providing a potential therapeutic target for ischemic stroke. View Full-Text
Keywords: cerebral ischemic injury; ischemic stroke; miRNA-378; apoptosis; caspase-3 cerebral ischemic injury; ischemic stroke; miRNA-378; apoptosis; caspase-3
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Zhang, N.; Zhong, J.; Han, S.; Li, Y.; Yin, Y.; Li, J. MicroRNA-378 Alleviates Cerebral Ischemic Injury by Negatively Regulating Apoptosis Executioner Caspase-3. Int. J. Mol. Sci. 2016, 17, 1427.

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