Circular RNA expression profile in blood according to ischemic stroke etiology

Abstract

Background: 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. Methods: A comprehensive expression profile of blood circRNAs was conducted by Arraystar Human circRNA arrays (13,617 probes) on a discovery cohort of 30 stroke patients with different stroke etiologies by TOAST classification. Real-time quantitative PCR (RT-qPCR) was used to validate array results in a cohort of 50 stroke patients. Functional in silico analysis was performed to identify potential interactions with microRNAs (miRNAs) and pathways underlying deregulated circRNAs. Results: A set of 60 circRNAs were found to be upregulated in atherotrombotic versus cardioembolic strokes (foldchange > = 1.5 and p-value ≤ 0.05). Differential expression of hsa_circRNA_102488, originated from UBA52 gene, was replicated in the validation cohort. RNA-binding proteins (RBPs) sites of hsa_circRNA_102488 clustered around AGO2 and FUS proteins. Further functional analysis revealed interactions between deregulated circRNAs and a set of miRNAs involved in stroke-related pathways, such as fatty acid biogenesis or lysine degradation. Conclusion: Different stroke subtypes show specific profiles of circRNAs expression. circRNAs may serve as a new source of biomarkers of stroke etiology in acute ischemic stroke patients.

Monocyte Transmodulation: The Next Novel Therapeutic Approach in Overcoming Ischemic Stroke?

“…Studies have recently been conducted in the field of stroke regarding the use of RNA in peripheral blood (136). These studies are supported by clinical applications in the diagnosis of diseases, such as myocardial infarction (137) and cancer (138).…”

RNA-seq Identifies circRNAs Expression Profiles and Potential Biomarkers for Intracerebral Hemorrhage

“…AGO2 is associated with the miRNA pro le in the brain of a rat stroke model [61]. AGO2, FUS, HuR and EIF4A3 were reported to have potential roles in IS [21], but their roles in ICH have never been reported. FMR1 and U2AF2 are involved in human neural cells and regulates the development of neural cells [62], DGCR8 is involved in the development of neuropsychiatric disorders and glioma cells [63,64].…”

“…These characteristics make circRNAs promising biomarkers in many human diseases [14]. In the stroke eld, circRNA expression pro le changes in IS have been described, supporting circRNAs as potential biomarkers and therapeutic targets in IS [21][22][23][24][25]. Additionally, two recent studies revealed that the circRNA expression pro les signi cantly changed after ICH in rat brain tissues [26,27].…”

“…Lysine participates in the crosslinking of collagen and plays essential roles in the metabolism of fatty acids [58]. Lysine degradation and fatty acid metabolism were considered as independent predictors of ischemic stroke events [21,59]. Similar roles might also exist in ICH.…”

“…There is growing evidence that circRNAs could serve as potential biomarkers in peripheral blood in coronary artery disease, early preeclampsia and cancers [16][17][18][19][20]. Moreover, multiple recent studies have reported circRNA expression pro les changed in ischemic stroke (IS) [21][22][23][24][25], suggesting that circRNAs are potential biomarkers and therapeutic targets in IS. In addition, two recent studies reported that circRNA expression pro les are altered after ICH in rat brain tissue [26,27].…”