Ischemic stroke (IS) remains a major cause of disability and death. The changes in long non-coding RNA (lncRNA) RGD1566344 expression in the mouse cerebral cortex, including the infarct and penumbra regions after IS, are not clear. Less is known about the impact and underlying mechanisms of RGD1566344 in IS. In this study, we found that RGD1566344 levels were elevated in the ischemic infarct and penumbra regions 12 h after middle cerebral artery occlusion/reperfusion (MCAO/R) in male mice and in PC12 cells with oxygen glucose deprivation/reperfusion (OGD/R). The inhibition of RGD1566344 by small interference RNA (siRNA) significantly alleviated apoptosis in OGD/R PC12 cells. In cell transfection, quantitative real-time PCR, and Western blot experiments, we demonstrated the possible interaction of non-POU domain-containing octamer-binding protein (NONO) with RGD1566344. The NONO level in OGD/R PC12 cells was obviously increased after inhibiting the RGD1566344 treatment; subsequently the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was activated. This demonstrated the effect of the RGD1566344-NONO-AKT axis on neural protection after IS. These results revealed a new molecular mechanism of lncRNA RGD1566344 inhibitors through targeting NONO/AKT/mTOR signaling to protect against ischemic neuronal injury, providing strong evidence for the development of promising therapeutic strategies against IS.

中文翻译：

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局灶性脑缺血再灌注后雄性小鼠脑皮质中长非编码 RNA RGD1566344 的表达以及非编码 RNA RGD1566344 抑制剂的神经保护作用。


缺血性中风（IS）仍然是导致残疾和死亡的主要原因。 IS后小鼠大脑皮层（包括梗死区和半影区）长非编码RNA（lncRNA）RGD1566344表达的变化尚不清楚。关于 RGD1566344 在 IS 中的影响和潜在机制知之甚少。在这项研究中，我们发现雄性小鼠大脑中动脉闭塞/再灌注（MCAO/R）12小时后以及氧糖剥夺/再灌注（OGD/R）的PC12细胞中缺血性梗塞和半暗带区域的RGD1566344水平升高。小干扰 RNA (siRNA) 对 RGD1566344 的抑制可显着减轻 OGD/R PC12 细胞的凋亡。在细胞转染、实时定量PCR和Western blot实验中，我们证明了不含POU结构域的八聚体结合蛋白（NONO）与RGD1566344可能存在相互作用。抑制RGD1566344处理后OGD/R PC12细胞中NONO水平明显升高；随后蛋白激酶 B (AKT)/哺乳动物雷帕霉素靶蛋白 (mTOR) 信号通路被激活。这证明了 RGD1566344-NONO-AKT 轴对 IS 后神经保护的作用。这些结果揭示了lncRNA RGD1566344抑制剂通过靶向NONO/AKT/mTOR信号传导来预防缺血性神经元损伤的新分子机制，为开发有前景的IS治疗策略提供了有力的证据。