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

miR-328-3p 是中风的预测因子,可加重脑缺血再灌注损伤

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作者:Shun Wang, Jiang Jun, Liyuan Cong, Lutao Du, Chuanxin Wang

Background

In the present study, we aimed to identify microRNAs (miRNAs) that affected the prognosis of stroke and assess their biological effects. Materials and

Conclusion

Our 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.

Methods

A 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.

Results

The 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.

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