New Drug Innovation and Development Institute, Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China; Department of Biomedical Engineering, School of Medicine and School of Engineering, The University of Alabama at Birmingham, USA.
New Drug Innovation and Development Institute, Department of Pharmacy, College of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, China.
Brain Res. 2019 Jul 1;1714:18-26. doi: 10.1016/j.brainres.2019.02.020. Epub 2019 Feb 16.
Brain stroke is one of the leading causes of death worldwide. We explored a potential stroke-related role for a newly found microRNA, miR-1247-3p, and one of its target genes, caspase-2, predicted by TargetScanVert. In the present study, we found that miR-1247-3p was downregulated during ischemia/reperfusion (I/R) and that LV-miR-1247-3p overexpression attenuated brain impairment induced by I/R. Similar results were observed in neuro2a (N2a) cells treated with oxygen-glucose deprivation/reoxygenation (OGD/R). Caspase-2 was upregulated in the I/R and OGD/R model, while Z-VDVAD-FMK - the inhibitor of caspase-2-inhibited apoptosis of N2a cells induced by OGD/R. An miR-1247-3p mimic inhibited caspase-2 expression and attenuated apoptosis of N2a cells induced by OGD/R. Myocardin-related transcription factor-A (MRTF-A) overexpression upregulated miR-1247 and mature miR-1247-3p levels and attenuated apoptosis induced by OGD/R, whereas its anti-apoptotic function could be blocked by a miR-1247-3p inhibitor. Hence, we conclude that miR-1247-3p may protect cells during brain stroke. This study offers insights for the development of effective therapeutics for promoting the survival of cerebral neurons during brain I/R injury.
脑中风是全球主要的致死原因之一。我们探索了一种新发现的 microRNA，miR-1247-3p，及其靶基因 caspase-2 在中风相关方面的潜在作用，该靶基因是由 TargetScanVert 预测的。在本研究中，我们发现 miR-1247-3p 在缺血/再灌注（I/R）期间下调，并且 LV-miR-1247-3p 的过表达可减轻 I/R 引起的脑损伤。在接受氧葡萄糖剥夺/再氧合（OGD/R）处理的神经 2a（N2a）细胞中观察到类似的结果。在 I/R 和 OGD/R 模型中 caspase-2 上调，而 caspase-2 的抑制剂 Z-VDVAD-FMK 可抑制 OGD/R 诱导的 N2a 细胞凋亡。miR-1247-3p 模拟物抑制 caspase-2 的表达并减轻 OGD/R 诱导的 N2a 细胞凋亡。肌细胞增强因子 2A（MRTF-A）过表达上调 miR-1247 和成熟的 miR-1247-3p 水平，并减轻 OGD/R 诱导的细胞凋亡，而其抗凋亡功能可被 miR-1247-3p 抑制剂阻断。因此，我们得出结论，miR-1247-3p 可能在脑中风期间保护细胞。本研究为开发有效的治疗方法以促进脑 I/R 损伤期间大脑神经元的存活提供了思路。
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