Zhang, Rong, Zhou, Weipin, Yu, Zhijun, Yang, Ling, Liu, Guangqi, Yu, Haotian, Zhou, Qianyi, Min, Zhenli, Zhang, Chunxiang, Wu, Qingming, Hu, Xia-Min, and Yuan, Qiong
Highlights • miR-1247-3p can mediate apoptosis of neuronal in stroke. • Caspase-2 may be a target of miR-1247-3p. • Caspase-2 is involved in the apoptosis of neuronal induced by stroke. • MRTF-A can regulate miR-1247-3P expression. Abstract 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. [ABSTRACT FROM AUTHOR]