Lu Dan, Ho Eric S, Mai Hongcheng, Zang Jiankun, Liu Yanfang, Li Yufeng, Yang Bing, Ding Yan, Tsang Chi Kwan, Xu Anding
Department of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Clinical Neuroscience Institute, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Front Neurosci. 2020 Feb 6;14:81. doi: 10.3389/fnins.2020.00081. eCollection 2020.
Many hospitals lack facilities for accurate diagnosis of acute ischemic stroke (AIS). Circular RNA (circRNA) is highly expressed in the brain and is closely associated with stroke. In this study, we examined whether the blood-borne circRNAs could be promising candidates as adjunctive diagnostic biomarkers and their pathophysiological roles after stroke. We profiled the blood circRNA expression in mice subjected to experimental focal cerebral ischemia and validated the selected circRNAs in AIS patients. We demonstrated that 128, 198, and 789 circRNAs were significantly altered at 5 min, 3 h, and 24 h after ischemic stroke, respectively. Our bioinformatics analysis revealed that the circRNA-targeted genes were associated with the Hippo signaling pathway, extracellular matrix-receptor interaction, and fatty acid metabolism at 5 min, 3 h and 24 h after ischemic stroke, respectively. We verified that many of these circRNAs existed in the mouse brain. Furthermore, we found that most of the predicted circRNA-miRNA interactions apparently exhibited functional roles in terms of regulation of their target gene expression in the brain. We also verified that many of these mouse circRNAs were conserved in human. Finally, we found that circBBS2 and circPHKA2 were differentially expressed in the blood of AIS patients. These results demonstrate that blood circRNAs may serve as potential biomarkers for AIS diagnosis and reveal the pathophysiological responses in the brain after ischemic stroke.
许多医院缺乏准确诊断急性缺血性中风（AIS）的设备。环状RNA（circRNA）在大脑中高表达，且与中风密切相关。在本研究中，我们检测了血源性circRNA是否有望作为辅助诊断生物标志物及其在中风后的病理生理作用。我们分析了实验性局灶性脑缺血小鼠的血液circRNA表达，并在AIS患者中验证了所选的circRNA。我们发现，在缺血性中风后5分钟、3小时和24小时，分别有128、198和789种circRNA发生了显著变化。我们的生物信息学分析表明，circRNA靶向的基因在缺血性中风后5分钟、3小时和24小时分别与Hippo信号通路、细胞外基质-受体相互作用和脂肪酸代谢相关。我们证实这些circRNA中的许多存在于小鼠大脑中。此外，我们发现大多数预测的circRNA- miRNA相互作用在调节其大脑中靶基因表达方面显然发挥了功能作用。我们还证实这些小鼠circRNA中的许多在人类中是保守的。最后，我们发现circBBS2和circPHKA2在AIS患者血液中差异表达。这些结果表明，血液circRNA可能作为AIS诊断的潜在生物标志物，并揭示缺血性中风后大脑中的病理生理反应。
