Namous Hadjer, Arruri Vijay, Galleske Thomas, Vemuganti Raghu
Department of Neurological Surgery, University of Wisconsin-Madison, Madison, WI, USA.
Department of Neurological Surgery, University of Wisconsin-Madison, Madison, WI, USA; William S. Middleton Memorial Veterans Administration Hospital, Madison, WI, USA.
Exp Neurol. 2025 Jul 9;393:115372. doi: 10.1016/j.expneurol.2025.115372.
Super enhancer RNAs (seRNAs) serve as vital regulators of gene expression, yet their role in ischemic stroke remains unexplored. Using microarrays, we profiled seRNAs and their target mRNAs in the peri-infarct cortex of male and female C57BL/6 J mice at 6 h and 24 h of reperfusion after transient focal ischemia. The seRNA expression profiles altered in a temporal and sex-specific manner with a more pronounced dysregulation in males. Gene ontology analysis showed that stroke-responsive seRNA-associated mRNAs involved in critical pathways, including neurogenesis, angiogenesis, and immune responses. Weighted Gene Co-expression Network Analysis showed that the upregulated driver seRNAs are associated with leukocyte proliferation and inflammation, and the downregulated driver seRNAs are linked to nucleosome organization, RNA stability, neuronal apoptosis, and mTOR signaling after focal ischemia. Several stroke-responsive seRNAs are also observed to be associated with transcription factors. These results suggest that seRNAs are pivotal regulators of post-stroke brain damage and recovery, providing potential targets for therapeutic intervention.
超级增强子RNA（seRNAs）是基因表达的重要调节因子，但其在缺血性中风中的作用仍未得到探索。我们使用微阵列技术，对雄性和雌性C57BL/6 J小鼠短暂局灶性缺血再灌注6小时和24小时后梗死灶周围皮质中的seRNAs及其靶标mRNA进行了分析。seRNA表达谱以时间和性别特异性方式改变，雄性小鼠的失调更为明显。基因本体分析表明，中风反应性seRNA相关的mRNA参与了关键途径，包括神经发生、血管生成和免疫反应。加权基因共表达网络分析表明，上调的驱动seRNAs与白细胞增殖和炎症相关，下调的驱动seRNAs与局灶性缺血后的核小体组织、RNA稳定性、神经元凋亡和mTOR信号传导有关。还观察到几种中风反应性seRNAs与转录因子有关。这些结果表明，seRNAs是中风后脑损伤和恢复的关键调节因子，为治疗干预提供了潜在靶点。
