miR-1247-3p mediates apoptosis of cerebral neurons by targeting caspase-2 in stroke
Autor: | Rong Zhang, Qian-Yi Zhou, Chunxiang Zhang, Weipin Zhou, Zhijun Yu, Ling Yang, Qiong Yuan, Guangqi Liu, Zhen-Li Min, Qing-Ming Wu, Xiamin Hu, Haotian Yu |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Caspase 2 Ischemia Down-Regulation Apoptosis Cell Line 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Transcription (biology) microRNA medicine Animals Molecular Biology Gene Neurons biology Chemistry General Neuroscience Nuclear Proteins Infarction Middle Cerebral Artery medicine.disease Mice Inbred C57BL Oxygen Stroke MicroRNAs 030104 developmental biology Glucose Reperfusion Injury Cancer research biology.protein Trans-Activators Neurology (clinical) 030217 neurology & neurosurgery Developmental Biology Signal Transduction |
Zdroj: | Brain research. 1714 |
ISSN: | 1872-6240 |
Popis: | 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. |
Databáze: | OpenAIRE |
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