Circular RNA expression alterations are involved in OGD/R-induced neuron injury
Circular RNA expression alterations are involved in OGD/R-induced neuron injury
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DOI：
10.1016/j.bbrc.2016.01.183
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发表时间：
2016-02-26
影响因子：
3.1
通讯作者：
Ma, Qiu-Jie
中科院分区：
文献类型：
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作者：
Lin, Shao-Peng;Ye, Shan;Ma, Qiu-Jie
脑缺血再灌注损伤（IRI）是临床常见的病理过程，是导致缺血性器官进一步损伤的关键步骤。脑IRI的机制仍未完全清楚，导致缺乏有效的治疗方法。研究表明，circular RNA（circRNA）可作为miRNA海绵，通过circRNA-miRNA基因通路在基因表达调控中发挥重要作用。然而，circRNA在脑IRI发病机制中的具体作用仍不清楚。因此，在本研究中，我们研究了HT 22细胞在氧葡萄糖剥夺/复氧（OGID/R）和正常对照组中circRNA表达的差异。circRNA微阵列结果显示，与对照组相比，OGD/R模型中有15种circRNA发生显著改变（p < 0.05）。其中3例表达显著上调，12例表达下调。此外，使用定量实时聚合酶链反应（qRT-PCR）验证mmu-circRNA-015947的上调表达。生物信息学分析显示，mmu-circRNA-015947的上调表达可与miRNAs（mmu-miR-188- 3 p、mmu-miR-329- 5 p、mmu-miR-3057- 3 p、mmu-miR-5098和mmu-miR-683）相互作用，从而增强靶基因的表达。KEGG通路分析预测mmu-circRNA-015947可能参与已知参与IRI发病机制的代谢相关、代谢相关和免疫相关通路。本研究提示mmu-circRNA-015947的重叠表达可能参与了脑IRI的过程，为临床治疗提供了新的分子靶点。(C)2016 Elsevier Inc. All rights reserved.
Cerebral ischemia-reperfusion injury (IRI) is a common clinical pathological process, and it is a key step in causing further ischemic organ damage. The mechanism of cerebral IRI is still not fully understood, leading to a lack of effective treatment. It has been demonstrated that circular RNAs (circRNAs) can act as miRNA sponges and play an important role in regulating gene expression through a circRNA-miRNAgene pathway. The specific role of circRNAs in the pathogenesis of cerebral IRI, however, is still unclear. Thus, in the present study, we investigated circRNA expression differences in HT22 cells with oxygen glucose deprivationireoxygenation (OGID/R) versus normal controls. The results from circRNA microarrays revealed that 15 circRNAs were significantly altered in the OGD/R model (p < 0.05) compared with the control group. Among them, 3 were significantly up-regulated, and the other 12 were down-regulated. Furthermore, the up-regulated expression of mmu-circRNA-015947 was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics analysis revealed that up regulated expression of mmu-circRNA-015947 could interact with miRNAs (mmu-miR-188-3p, mmu-miR-329-5p, mmu-miR-3057-3p, mmu-miR-5098 and mmu-miR-683) and thereby enhance target gene expression. KEGG pathway analysis predicted that mmu-circRNA-015947 may participate in apoptosis-related, metabolism-related and immune-related pathways, which are known to be involved in the pathogenesis of IRI. This research suggests that the overlapping expression of mmu-circRNA-015947 might be involved in the process of cerebral IRI and presents a novel molecular target for clinical therapy. (C) 2016 Elsevier Inc. All rights reserved.