Mozgovoy Ivan V, Shpetko Yana Yu, Denisova Alina E, Stavchansky Vasily V, Vinogradina Margarita A, Gubsky Leonid V, Dergunova Lyudmila V, Limborska Svetlana A, Filippenkov Ivan B
National Research Centre "Kurchatov Institute", Moscow, 123182, Russia.
Pirogov Russian National Research Medical University, Moscow, 117997, Russia.
Biochemistry (Mosc). 2025 May;90(5):568-581. doi: 10.1134/S0006297925600280.
Circular RNAs (circRNAs) are covalently closed non-coding RNAs with an increased metabolic stability, capable of regulating gene expression. CircRNAs can be potentially used as biomarkers and therapeutic targets in various diseases, including ischemic stroke. Transient middle cerebral artery occlusion (tMCAO) is commonly used as a model in stroke transcriptomics. Here, we used genome-wide RNA sequencing to investigate expression profiles of circRNAs in the frontal cortex of rats 24 h after tMCAO. Sixty-four differentially expressed circRNAs (fold change > 1.5; < 0.05) were identified; most of them were upregulated compared to sham-operated animals. According to on the MRI data, the analyzed region of the frontal cortex included the penumbra, an area containing damaged but viable cells, whose survival is crucial for the poststroke recovery. Based on bioinformatics analysis of identified circRNAs and previously obtained data on differential mRNA expression in this brain region, we predicted regulatory circRNA-microRNA-mRNA networks involved in ischemic stroke. Functional analysis of these networks revealed that genes whose expression in ischemia was presumably regulated by circRNAs, are involved in synaptic signaling and inflammatory response. Our data indicate a significant role of circRNA-mediated transcriptome regulation in the penumbra region in ischemia and suggest circRNA as potential targets in the development of new strategies in the therapy of stroke and poststroke complications.
环状RNA(circRNAs)是具有更高代谢稳定性的共价闭合非编码RNA,能够调节基因表达。CircRNAs在包括缺血性中风在内的各种疾病中有可能用作生物标志物和治疗靶点。短暂性大脑中动脉闭塞(tMCAO)通常用作中风转录组学的模型。在此,我们使用全基因组RNA测序来研究tMCAO后24小时大鼠额叶皮质中circRNAs的表达谱。鉴定出64种差异表达的circRNAs(倍数变化>1.5;<0.05);与假手术动物相比,其中大多数上调。根据MRI数据,额叶皮质的分析区域包括半暗带,这是一个包含受损但仍存活细胞的区域,其存活对中风后恢复至关重要。基于对鉴定出的circRNAs的生物信息学分析以及先前在该脑区获得的差异mRNA表达数据,我们预测了参与缺血性中风的调控circRNA-微小RNA-mRNA网络。对这些网络的功能分析表明,其表达在缺血中可能受circRNAs调控的基因参与突触信号传导和炎症反应。我们的数据表明circRNA介导的转录组调控在缺血半暗带区域中起重要作用,并提示circRNA作为开发中风及中风后并发症治疗新策略的潜在靶点。