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

Abstract

Background In the present study, we aimed to identify microRNAs (miRNAs) that affected the prognosis of stroke and assess their biological effects. Materials and 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 cm 3 ( 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. 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.

Extracellular vesicles containing anti-miR-128-3p derived from mesenchymal stem cells attenuate cerebral ischemia-reperfusion injury by suppressing neuronal pyroptosis and modulating microglia polarization

“…Neuron-derived exosomes with upregulated miR-21-5p could promote microglia M1 polarization [29]. Meanwhile, wang et al found that miR-128-3p level was upregulated in serum exosomes of stroke patients compared to healthy controls [16]. In this research, we found that miR-128-3p level was elevated in serum samples from patients with stroke compared with to healthy controls.…”

“…Qian et al showed that MSC-derived extracellular vesicles containing miR-140-5p attenuated brain injury in mice with subarachnoid hemorrhage via inhibition of microglia M1 activation [15]. Meanwhile, miR-128-3p level was found to be upregulated in serum exosomes of stroke patients [16]. In addition, downregulation of miR-128-3p was able to aggravate the infarct volume of brain tissues in MCAO mice [17].…”

Identification and Validation of Novel Potential Pathogenesis and Biomarkers to Predict the Neurological Outcome after Cardiac Arrest

“…Studies on PSMD14 were mainly associated with tumors, for example, targeting PSMD14 inhibited melanoma growth through SMAD3 stabilization [ 38 ]. Previously, Wang et al used miRNA-seq to identify miRNAs in the sera of stroke patients that could influence patient prognosis, and the results of this study showed that miR-328-3p levels were an independent correlate of short-term prognosis [ 39 ]. Generally, the close association of these genes with the nervous system suggests that the relationship between the expression status of these genes and the prognosis of the disease is worth investigating.…”

Emerging roles of extracellular vesicle-associated non-coding RNAs in hypoxia: Insights from cancer, myocardial infarction and ischemic stroke

“…Hence, miR-133a, which was found to be abundant in cancer EVs at low concentration, reduced tumor cell proliferation, survival, migration and metastasis in gastric carcinoma and colorectal carcinoma [136,238], whereas miR-133a-3p and miR-133b promoted cardiomyocyte survival and neuronal plasticity in myocardial infarction and stroke, respectively, and enhanced functional tissue recovery [162,195,196]. Likewise, miR-328b-3p promoted tumor cell proliferation, migration, invasion and tumor growth in lung carcinoma [105], whereas miR-328b-3p augmented cardiomyocyte death and apoptosis in myocardial infarction [148] and augmented neuronal death and neuroinflammation in ischemic stroke [239]. Besides, EV-associated miR-361 promoted tumor cell proliferation and survival in colorectal carcinoma [103] and neuronal survival in ischemic stroke [217], whereas cardiac-specific miR-361 overexpression reduced cardiomyocyte survival by increasing mitochondrial fission in myocardial infarction [240].…”

“…Promotes tumor cell proliferation, migration, invasion and epithelial -mesenchymal transition; promotes tumor growth [105] Augments cardiomyocyte death and apoptosis [148] [miR-328-3p agomir augments neuronal death, neurological deficits, brain neutrophil invasion and proinflammatory cytokine levels [239]…”