Circ-camk4 involved in cerebral ischemia/reperfusion induced neuronal injury

Stroke and subsequent cerebral ischemia/reperfusion (I/R) injury is a frequently occurring disease that can have serious consequences in the absence of timely intervention. Circular RNAs (circRNAs) in association with microRNAs (miRNAs) and RNA-binding proteins (RBPs) can influence gene expression....

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Bibliographic Details
Published in:Scientific reports 2020-04, Vol.10 (1), p.7012-7012, Article 7012
Main Authors: Zhang, Zhao-Huan, Wang, Yue-Rong, Li, Fei, Liu, Xiu-Ling, Zhang, Hui, Zhu, Zhong-Zheng, Huang, Hai, Xu, Xiao-Hui
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Bioinformatics
Brain injury
Calcium-Calmodulin-Dependent Protein Kinase Type 4 - genetics
Calcium-Calmodulin-Dependent Protein Kinase Type 4 - metabolism
Cell death
Cell Line
Cerebral Arterial Diseases - genetics
Cerebral Arterial Diseases - metabolism
Cerebral blood flow
Cerebral cortex
Computational Biology
Gene expression
Glucose
Glutamatergic transmission
Humans
Ischemia
Latency
Male
MAP kinase
miRNA
Nervous System Diseases - genetics
Nervous System Diseases - metabolism
Next-generation sequencing
Oxygen
Rats
Rats, Sprague-Dawley
Reperfusion
Reperfusion Injury - genetics
Reperfusion Injury - metabolism
RNA, Circular - genetics
RNA, Circular - metabolism
RNA-binding protein
Signal transduction
Stroke
Stroke - genetics
Stroke - metabolism
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Summary:Stroke and subsequent cerebral ischemia/reperfusion (I/R) injury is a frequently occurring disease that can have serious consequences in the absence of timely intervention. Circular RNAs (circRNAs) in association with microRNAs (miRNAs) and RNA-binding proteins (RBPs) can influence gene expression. However, whether circRNAs have a role in cerebral I/R injury pathogenesis, especially soon after onset, is unclear. In this study, we used the SD rat middle cerebral artery occlusion (MCAO) model of stroke to examine the role of circRNAs in cerebral I/R injury. We used high-throughput sequencing (HTS) to compare the expression levels of circRNAs in cerebral cortex tissue from MCAO rats during the occlusion-reperfusion latency period 3 hours after I/R injury with those in control cerebral cortices. Our sequencing results revealed that expression levels of 44 circRNAs were significantly altered after I/R, with 16 and 28 circRNAs showing significant up- and down-regulation, respectively, relative to levels in control cortex. We extended these results in vitro in primary cultured neuron cells exposed to oxygen-glucose deprivation/reperfusion (OGD/R) using qRT-PCR to show that levels of circ-camk4 were increased in OGD/R neurons relative to control neurons. Bioinformatics analyses predicted that several miRNAs could be associated with circ-camk4 and this prediction was confirmed in a RNA pull-down assay. KEGG analysis to predict pathways that involve circ-camk4 included the glutamatergic synapse pathway, MAPK signaling pathway, and apoptosis signaling pathways, all of which are known to be involved in brain injury after I/R. Our results also demonstrate that levels of the human homolog to circ-camk4 (hsa-circ-camk4) are elevated in SH-SY5Y cells exposed to OGD/R treatment. Overexpression of hsa-circ-camk4 in SH-SY5Y cells significantly increased the rate of cell death after OGD/R, suggesting that circ-camk4 may play a key role in progression of cerebral I/R injury.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-63686-1