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大脑中动脉闭塞(MCAO)小鼠不同缺血皮层中RNA表达谱的系统分析

Systematic Analysis of RNA Expression Profiles in Different Ischemic Cortices in MCAO Mice.

作者信息

Zang Jiankun, Tang Xionglin, Su Xuanlin, Zhang Tianyuan, Lu Dan, Xu Anding

机构信息

Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 West Huangpu Ave, Guangzhou, 510632, China.

Clinical Neuroscience Institute, The First Affiliated Hospital of Jinan University, Guangzhou, China.

出版信息

Cell Mol Neurobiol. 2023 Mar;43(2):859-878. doi: 10.1007/s10571-022-01220-9. Epub 2022 Apr 21.

Abstract

The prognosis of ischemic stroke patients is highly associated with the collateral circulation. And the competing endogenous RNAs (ceRNAs) generated from different compensatory supply regions may also involve in the regulation of ischemic tissues prognosis. In this study, we found the apoptosis progress of ischemic neurons in posterior circulation-supplied regions (close to PCA, cortex2) was much slower than that in anterior circulation-supplied territory (close to ACA, cortex1) in MCAO-3-h mice. Using the RNA sequencing and functional enrichment analysis, we analyzed the difference between RNA expression profile in cortex1 and cortex2 and the related biological processes. The results indicated that the differential expressed ceRNAs in cortex1 were involved in cell process under acute injury, while the differential expressed ceRNAs in cortex2 was more likely to participate in long-term injury and repair process. Besides, by establishing the miRNA-ceRNA interaction network we further sorted out two specifically distributed miRNAs, namely mmu-miR446i-3p (in cortex1) and mmu-miR3473d (in cortex2). And the specifically increased mmu-miR3473d in cortex2 mainly involved the angiogenesis and cell proliferation after ischemic stroke, which may be the critical reason for the longer therapeutic time window in cortex2. In conclusion, the present study reported the specific changes of ceRNAs in distinct compensatory regions potentially involved in the evolution of cerebral ischemic tissues and the unbalance prognosis after stroke. It provided more evidence for the collateral compensatory effects on patients' prognosis and carried out the new targets for the ischemic stroke therapy.

摘要

缺血性中风患者的预后与侧支循环高度相关。并且,来自不同代偿供应区域产生的竞争性内源性RNA(ceRNA)也可能参与缺血组织预后的调控。在本研究中,我们发现,在大脑中动脉闭塞3小时的小鼠中,后循环供应区域(靠近大脑后动脉,皮质2)缺血神经元的凋亡进程比前循环供应区域(靠近大脑前动脉,皮质1)的要慢得多。通过RNA测序和功能富集分析,我们分析了皮质1和皮质2中RNA表达谱的差异以及相关生物学过程。结果表明,皮质1中差异表达的ceRNA参与急性损伤下的细胞进程,而皮质2中差异表达的ceRNA更有可能参与长期损伤和修复过程。此外,通过建立miRNA-ceRNA相互作用网络,我们进一步筛选出两个特异性分布的miRNA,即mmu-miR446i-3p(在皮质1中)和mmu-miR3473d(在皮质2中)。并且,皮质2中特异性增加的mmu-miR3473d主要参与缺血性中风后的血管生成和细胞增殖,这可能是皮质2中治疗时间窗更长的关键原因。总之,本研究报道了不同代偿区域中ceRNA的特异性变化,其可能参与脑缺血组织的演变和中风后预后的不平衡。它为侧支循环对患者预后的代偿作用提供了更多证据,并为缺血性中风治疗开辟了新靶点。

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Noncoding RNAs in ischemic stroke: time to translate.非编码 RNA 与缺血性脑卒中:是时候转化了。
Ann N Y Acad Sci. 2018 Jun;1421(1):19-36. doi: 10.1111/nyas.13612. Epub 2018 Apr 23.

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