MiR-328-3p, a Predictor of Stroke, Aggravates the Cerebral Ischemia-Reperfusion Injury.

Abstract

BackgroundIn the present study, we aimed to identify microRNAs (miRNAs) that affected the prognosis of stroke and assess their biological effects.Materials and MethodsA high-throughput sequencing (HTS) analysis was performed to screen distinctive miRNAs in serum exosomes of stroke patients, and these miRNAs were subsequently validated using individual quantitative real-time polymerase chain reaction (qRT-PCR) in a cohort consisting of 39 stroke patients and 20 normal controls. Briefly, miR-328-3p agomir or agomir NC was injected into rats before ischemia and reperfusion (I/R) injury. Zea-Longa score, neurological severity score (mNSS), triphenyltetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, transmission electron microscopy, and hematoxylin and eosin (H&E) staining were used to examine the brain injury. Immunohistochemistry was utilized to determine the expressions of TNF-α and IL-6.ResultsThe expression of serum exosomal miR-328-3p was significantly reduced in patients with an infarct volume ≥10 cm3 (P=0.01). Serum exosomal miR-328-3p was associated with the short-term prognosis (P=0.02), and the level of miR-328-3p was an independent relative factor for short-term prognosis (OR 5.276, P=0.02). The sensitivity of miR-328-3p level higher than 1.24 to predict the severity of the patient’s 1-week prognosis was 70%, and the specificity was 83% (AUC=0.74, P=0.02). The mNSS was higher in the miR-328-3p agomir group compared with the agomir NC group (P=0.03). Neutrophil infiltration was more serious in the miR-328-3p agomir group.ConclusionOur study indicated that miR-328-3p played a critical predictive role in the short-term prognosis of stroke, and up-regulation of miR-328-3p aggravated cerebral I/R injury.