Circulating MicroRNA Profiling Identifies Distinct MicroRNA Signatures in Acute Ischemic Stroke and Transient Ischemic Attack Patients

Abstract

Transient ischemic attack (TIA) refers to a momentary neurologic deficit caused by focal cerebral, spinal or retinal ischemic insult. TIA is associated with a high risk of impending acute ischemic stroke (AIS), a neurologic dysfunction characterized by focal cerebral, spinal or retinal infarction. Understanding the differences in molecular pathways in AIS and TIA has merit for deciphering the underlying cause for neuronal deficits with long-term effects and high risks of morbidity and mortality. In this study, we performed comprehensive investigations into the circulating microRNA (miRNA) profiles of AIS (n = 191) and TIA (n = 61) patients. We performed RNA-Seq on serum samples collected within 24 hrs of clinical diagnosis and randomly divided the study populations into discovery and validation cohorts. We identified a panel of 11 differentially regulated miRNAs at FDR < 0.05. Hsa-miR-548c-5p, -20a-5p, -18a-5p, -484, -652-3p, -486-3p, -24-3p, -181a-5p and -222-3p were upregulated, while hsa-miR-500a-3p and -206 were downregulated in AIS patients compared to TIA patients. We also probed the previously validated gene targets of our identified miRNA panel to highlight the molecular pathways affected in AIS. Moreover, we developed a multivariate classifier with potential utilization as a discriminative biomarker for AIS and TIA patients. The underlying molecular pathways in AIS compared to TIA may be explored further in functional studies for therapeutic targeting in clinical translation.

Perspective and Therapeutic Potential of the Noncoding RNA–Connexin Axis

“…These MS stage-specific EV-derived miRNAs have potential predictive value [ 103 ]. Circulating miRNA profiles show features distinguishing transient ischemic attack (TIA) from acute ischemic stroke (AIS) [ 104 ]. Eleven miRNAs were differentially expressed in the sera of patients with TIA and AIS, which could help discriminate between these two diseases [ 104 ].…”

“…Circulating miRNA profiles show features distinguishing transient ischemic attack (TIA) from acute ischemic stroke (AIS) [ 104 ]. Eleven miRNAs were differentially expressed in the sera of patients with TIA and AIS, which could help discriminate between these two diseases [ 104 ]. Clinical trials of ncRNA therapeutics have exploited RNAi technology to directly suppress target mRNA.…”

Atherosclerosis and Its Related Laboratory Biomarkers

“…However, more studies on miRNAs are required to clarify their potential as a prognostic and diagnostic biomarker, to determine therapeutic opportunities and challenges, but also to overcome the limitations of miRNA application as therapeutic agents, including target specificity, safety, delivery, and efficiency [33,109,110].…”

Are Ischemic Stroke and Alzheimer’s Disease Genetically Consecutive Pathologies?

“…To date, there is a significant amount of data available on the differential expression of miRNAs in pathological conditions. For IS, miRNA profiles are provided in the blood of patients [114,115] and in brain tissues [116]. MiRNA profiles were also obtained for rats after tMCAO in the blood and in various tissues, including different areas of the brain [117].…”