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环状RNA表达改变参与氧糖剥夺/复氧诱导的神经元损伤。

Circular RNA expression alterations are involved in OGD/R-induced neuron injury.

作者信息

Lin Shao-Peng, Ye Shan, Long Youming, Fan Yongxiang, Mao Hai-Feng, Chen Mei-Ting, Ma Qiu-Jie

机构信息

Department of Emergency, The Second Affiliated Hospital of Guangzhou Medical University, 250# Changgang East Road, Guangzhou 510260, Guangdong Province, China.

Department of Geriatrics, The Second Affiliated Hospital of Guangzhou Medical University, 250# Changgang East Road, Guangzhou 510260, Guangdong Province, China.

出版信息

Biochem Biophys Res Commun. 2016 Feb 26;471(1):52-6. doi: 10.1016/j.bbrc.2016.01.183. Epub 2016 Feb 2.

Abstract

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-miRNA-gene 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 deprivation/reoxygenation (OGD/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.

摘要

脑缺血再灌注损伤(IRI)是一种常见的临床病理过程,是导致缺血器官进一步损伤的关键步骤。脑IRI的机制仍未完全阐明,导致缺乏有效的治疗方法。已有研究表明,环状RNA(circRNA)可作为微小RNA(miRNA)的海绵,并通过circRNA-miRNA-基因途径在调节基因表达中发挥重要作用。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,我们研究了氧糖剥夺/复氧(OGD/R)处理的HT22细胞与正常对照相比circRNA的表达差异。circRNA微阵列结果显示,与对照组相比,OGD/R模型中有15种circRNA发生了显著变化(p<0.05)。其中,3种显著上调,另外12种下调。此外,通过定量实时聚合酶链反应(qRT-PCR)验证了mmu-circRNA-015947的上调表达。生物信息学分析表明,mmu-circRNA-015947的上调表达可与miRNA(mmu-miR-188-3p、mmu-miR-329-5p、mmu-miR-3057-3p、mmu-miR-5098和mmu-miR-683)相互作用,从而增强靶基因表达。KEGG通路分析预测,mmu-circRNA-015947可能参与凋亡相关、代谢相关和免疫相关通路,这些通路已知与IRI的发病机制有关。本研究表明,mmu-circRNA-015947的重叠表达可能参与脑IRI过程,并为临床治疗提供了一个新的分子靶点。

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