Circulating PIWI-interacting RNAs in Acute Ischemic Stroke patients

Background: Stroke refers to an abrupt neurological deficit, caused by an acute focal injury of the central nervous system via infarction or hemorrhage due to impaired vascularity, and remains among the leading causes of disability and death worldwide. Stroke is often preceded by an episode of neuronal deficit termed transient ischemic attack (TIA), which presents an effective opportunity for mitigating the risk of an eminent acute ischemic stroke (AIS). Circulating non-coding RNAs (ncRNAs) have emerged as important biomarkers for stroke, but PIWI-interacting RNAs (piRNAs), a class of small regulatory ncRNAs, have not been previously explored as diagnostic or prognostic biomarkers for stroke. Methods: We conducted comprehensive circulating piRNA profiling of AIS and TIA patients using RNA-seq on serum samples collected within 24 h of clinical diagnosis. The study cohort was divided into discovery and cross-validation datasets to identify replicated piRNAs using stringent analysis cut-offs. The expression levels of the panel of differentially regulated piRNAs between AIS and TIA patients were also compared with healthy controls. Results: We identified a panel of 10 differentially regulated piRNAs between AIS and TIA patients; hsa-piR-28272, -piR-32972, -piR-28247, -piR-24553, -piR-24552, -piR-28275, -piR-28707 and -piR-32882 were upregulated, while hsa-piR-23058 and -piR-23136 were downregulated in AIS patients. Moreover, these 10 piRNAs were also differentially expressed in AIS patients compared to healthy controls. In addition, we investigated the potential gene targets of the dysregulated piRNAs and their plausible involvement in pathophysiological processes affected in stroke. Conclusions: The imbalances in the circulating piRnome of AIS and TIA patients presented herein provide important insights into the roles of piRNAs following ischemic brain injury and potentially provide opportunities to mitigate stroke-induced mortality and morbidity.