Circular RNAs in Ischemic Stroke: Biological Role and Experimental Models

Abstract

Ischemic stroke is among the leading causes of morbidity, disability, and mortality worldwide. Despite the recent progress in the management of acute ischemic stroke, timely intervention still represents a challenge. Hence, strategies to counteract ischemic brain injury during and around the acute event are still lacking, also due to the limited knowledge of the underlying mechanisms. Despite the increasing understanding of the complex pathophysiology underlying ischemic brain injury, some relevant pieces of information are still required, particularly regarding the fine modulation of biological processes. In this context, there is emerging evidence that the modulation of circular RNAs, a class of highly conserved non-coding RNA with a closed-loop structure, are involved in pathophysiological processes behind ischemic stroke, unveiling a number of potential therapeutic targets and possible clinical biomarkers. This paper aims to provide a comprehensive overview of experimental studies on the role of circular RNAs in ischemic stroke.

Serum-derived exosomal circENC1 inhibits SMC phenotypic switching to stabilize atherosclerotic plaques by interacting with miR-513a-5p and inhibiting MYH9 degradation

“…For example, stimulation of serum-exos by oxidized low-density lipoprotein (oxLDL), hyperglycemia or hypertension, which are established risk factors for atherosclerotic vulnerable plaques, can lead to the upregulation of inflammation-and proliferationrelated genes within exosomes and exert corresponding functional effects [10][11][12][13] . Notably, previous research and our sequencing analysis revealed that suppression of SMC phenotypic switching-related genetic content was most significantly increased in serum-exos from patients with stable plaques (SPs) compared to those from patients with vulnerable plaques [14][15][16][17] , suggesting that the principal function of serum exosomes containing pertinent genetic content from SPs might be to regulate SMC phenotypic switching. Serum-exos are characterized by biocompatibility, low immunogenicity, and minimal adverse reactions 18,19 .…”

Preconditioning Concepts for the Therapeutic Use of Extracellular Vesicles Against Stroke

“…They are involved in the pathophysiological processes underlying ischemic stroke, and emerging evidence points to their potential as therapeutic targets and clinical biomarkers. 26 Indeed, in EVs derived from preconditioned sources, the researchers found an enhanced expression of the specific circRNA, circ-Rps5. They further elucidated the mechanistic pathway by which circ-Rps5 acts through downstream effects on SIRT7 and miR-124-3p, thereby modulating the shift in microglial phenotype.…”

Circulating microRNAs as diagnostic biomarkers for ischemic stroke: evidence from comprehensive analysis and real-world validation

“…Current diagnosis for IS is mainly based on the use of computed tomography scan or magnetic resonance imaging after the patient is hospitalized 2 . In the past decade, studies have emerged suggesting other potential diagnostic approaches for different diseases including the dysregulation of microRNAs (miRNAs) and circular RNAs 3 . miRNAs have become one of the most promising types of biomarkers among these approaches and were extensively studied for their potential use in cancers, nervous system disorders and cardiovascular diseases 4 .…”