Circular RNA expression profile in blood according to ischemic stroke etiology.

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Abstract

The discovery of novel biomarkers of stroke etiology would be most helpful in management of acute ischemic stroke patients. Recently, circular RNAs (circRNAs) have been proposed as candidate biomarkers of neurological conditions due to its high stability. circRNAs function as sponges, sequestering miRNAs and are involved in most relevant biological functions. Our aim was to identify differentially expressed circRNAs in acute ischemic stroke patients according to stroke etiology.

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The interaction of circRNAs and RNA binding proteins: An important part of circRNA maintenance and function

Jiankun Zang, Dan Lu, Anding Xu (2018)

The widespread expression of circular RNAs (circRNAs) is regarded as a feature of gene expression in highly diverged eukaryotes. Recent studies have shown that circRNAs can act as a miRNA sponge to repress miRNA function, participate in splicing of target genes, translate genes into protein and interact with RNA binding proteins (RBPs). RBPs are a broad class of proteins involved in gene transcription and translation, and interaction with RBPs is considered an important part of circRNA function, which can serve as an essential element underlying the functions of circRNAs, including genesis, translation, transcriptional regulation of target genes, and extracellular transport. In this mini-review, we attempt to explore in detail the relationship between circRNAs and RBPs, and the interactions between the two factors. The goal of this review is to investigate the emerging studies of RBPs and circRNAs to better understand how their interaction alters cellular function.

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Circular RNA DLGAP4 Ameliorates Ischemic Stroke Outcomes by Targeting miR-143 to Regulate Endothelial-Mesenchymal Transition Associated with Blood-Brain Barrier Integrity.

Ying Bai, Yuan Zhang, Bing Han … (2018)

Circular RNAs (circRNAs) are highly expressed in the CNS and regulate physiological and pathophysiological processes. However, the potential role of circRNAs in stroke remains largely unknown. Here, we show that the circRNA DLGAP4 (circDLGAP4) functions as an endogenous microRNA-143 (miR-143) sponge to inhibit miR-143 activity, resulting in the inhibition of homologous to the E6-AP C-terminal domain E3 ubiquitin protein ligase 1 expression. circDLGAP4 levels were significantly decreased in the plasma of acute ischemic stroke patients (13 females and 13 males) and in a mouse stroke model. Upregulation of circDLGAP4 expression significantly attenuated neurological deficits and decreased infarct areas and blood-brain barrier damage in the transient middle cerebral artery occlusion mouse stroke model. Endothelial-mesenchymal transition contributes to blood-brain barrier disruption and circDLGAP4 overexpression significantly inhibited endothelial-mesenchymal transition by regulating tight junction protein and mesenchymal cell marker expression. Together, the results of our study are illustrative of the involvement of circDLGAP4 and its coupling mechanism in cerebral ischemia, providing translational evidence that circDLGAP4 serves as a novel therapeutic target for acute cerebrovascular protection.SIGNIFICANCE STATEMENT Circular RNAs (circRNAs) are involved in the regulation of physiological and pathophysiological processes. However, whether circRNAs are involved in ischemic injury, particularly cerebrovascular disorders, remains largely unknown. Here, we demonstrate a critical role for circular RNA DLGAP4 (circDLGAP4), a novel circular RNA originally identified as a sponge for microRNA-143 (miR-143), in ischemic stroke outcomes. Overexpression of circDLGAP4 significantly attenuated neurological deficits and decreased infarct areas and blood-brain barrier damage in the transient middle cerebral artery occlusion mouse stroke model. To our knowledge, this is the first report describing the efficacy of circRNA injection in an ischemic stroke model. Our investigation suggests that circDLGAP4 may serve as a novel therapeutic target for acute ischemic injury.

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Mini Review: Circular RNAs as Potential Clinical Biomarkers for Disorders in the Central Nervous System

Dan Lu, An-Ding Xu (2016)

Circular RNAs (circRNAs) are a type of non-coding RNAs (ncRNAs), produced in eukaryotic cells during post-transcriptional processes. They are more stable than linear RNAs, and possess spatio-temporal properties. CircRNAs do not distribute equally in the neuronal compartments in the brain, but largely enriched in the synapses. These ncRNA species can be used as potential clinical biomarkers in complex disorders of the central nervous system (CNS), which is supported by recent findings. For example, ciRS-7 was found to be a natural microRNAs sponge for miRNA-7 and regulate Parkinson’s disease/Alzheimer’s disease-related genes; circPAIP2 is an intron-retaining circRNA which upregulates memory-related parental genes PAIP2 to affect memory development through PABP reactivation. The quantity of circRNAs carry important messages, either when they are inside the cells, or in circulation, or in exosomes released from synaptoneurosomes and endothelial. In addition, small molecules such as microRNAs and microvesicles can pass through the blood–brain barrier (BBB) and get into blood. For clinical applications, the study population needs to be phenotypically well-defined. CircRNAs may be combined with other biomarkers and imaging tools to improve the diagnostic power.