Screening circular RNA expression patterns following focal cerebral ischemia in mice
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Cuiying Liu1, Chencheng Zhang1, Jian Yang1, Xiaokun Geng1,2, Huishan Du1,2, Xunming Ji1,3 and Heng Zhao1,4
1China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China
2Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, China
3Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
4Department of Neurosurgery, Stanford University, Stanford, CA, USA
Heng Zhao, email: [email protected]
Xunming Ji, email: [email protected]
Keywords: stroke, middle cerebral artery occlusion, circular RNA, microRNA, microarray
Received: April 21, 2017 Accepted: August 07, 2017 Published: September 23, 2017
Circular RNAs (circRNAs) have been demonstrated to act as microRNA (miRNA) sponges and they play important roles in regulating gene expression through a circRNA-miRNA-gene pathway. The specific roles of circRNAs in the pathogenesis of cerebral ischemia, however, are still unclear. Thus, the aim of this study is to determine circRNA expression profiles in the ischemic brain after stroke, which was induced by 45 min of transient middle cerebral artery occlusion (MCAO). The results from the circRNA microarrays revealed that 1027 circRNAs were significantly altered 48 hours after reperfusion in the ischemic brain compared with the sham group. Among them, 914 circRNAs were significantly upregulated, and the remaining 113 were significantly downregulated. In addition, the expressions of the three selected circRNAs, mmu_circRNA_40001, mmu_circRNA_013120, and mmu_circRNA_40806, were verified using quantitative real-time polymerase chain reaction (qRT-PCR). After predicting their target genes, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were further used to predict the associated significant cell signaling pathways and functions. The results show that the most enriched pathways are associated with the Rap1 signaling pathway and the Hippo signaling pathway, which regulate cell survival and death. Finally, we constructed an interaction network of circRNA-miRNA-target genes, including 13 miRNAs and their corresponding genes, indicating that changes in circRNA are associated with genes related with brain injury and recovery. In conclusion, circRNAs are complicated in the pathological development of brain injury after stroke, suggesting novel diagnostic and therapeutic targets for stroke therapy.
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