Abstract

Our previous study demonstrated that microRNA-424 (miR-424) protected against experimental stroke through inhibition of microglial proliferation and activation by targeting cell cycle proteins. The purpose of this study was to further explore the clinical significance of miR-424 in peripheral immune cells of patients with acute ischemic stroke (AIS). Blood samples were collected from 40 patients within 6 hours of symptom onset and 27 control subjects. MiR-424 levels in lymphocytes, neutrophils and plasma were determined by quantitative realtime-PCR. The diagnostic sensitivity and specificity of miR-424 for stroke was evaluated by receiver operator characteristic (ROC) curve. The correlation between miR-424 levels and clinical data was analyzed using Pearson’s correlation test. Plasma levels of inflammatory mediators (TNF-α, IL-10) and neurotrophic factor (IGF-1) were detected by ELISA. Notably, miR-424 expression levels in lymphocytes and neutrophils increased after stroke, suggestive of its diagnostic value in ischemic stroke. MiR-424 levels in neutrophils were negatively correlated with infarct volume. Lymphocytic miR-424 levels were negatively correlated with the number of lymphocytes and the expression of cyclin-dependent kinase CDK6. Moreover, plasma TNF-α and IGF-1 levels increased and decreased, respectively, in stroke patients, and miR-424 levels in lymphocytes and neutrophils were both inversely correlated with plasma TNF-α, IL-10, or IGF-1 levels. In summary, miR-424 levels in peripheral immune cells has diagnostic potential for ischemic stroke, and might affect the severity of acute stroke by depressing the peripheral inflammatory response through CDK6-dependent pathway in lymphocytes or CDK6-independent pathway neutrophils.

Highlights

  • Our previous study demonstrated that microRNA-424 protected against experimental stroke through inhibition of microglial proliferation and activation by targeting cell cycle proteins

  • To assess the role of miR-424 in stroke severity, we examined the correlation between miR-424 levels and brain infarct volume, and a negative linear correlation was found between miR-424 levels in neutrophils and brain infarct volume within 72 hours of stroke onset (Fig. 2A, p

  • This is the first report to investigate the clinical value of miR-424 in peripheral immune cells including lymphocytes, neutrophils and plasma from the acute ischemic stroke patients

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Summary

Introduction

Our previous study demonstrated that microRNA-424 (miR-424) protected against experimental stroke through inhibition of microglial proliferation and activation by targeting cell cycle proteins. MiR-424 levels in peripheral immune cells has diagnostic potential for ischemic stroke, and might affect the severity of acute stroke by depressing the peripheral inflammatory response through CDK6dependent pathway in lymphocytes or CDK6-independent pathway neutrophils. Further experimental research showed miR-424 levels in the brain remarkedly decreased at 24 hours postischemia and played a neuroprotective function against the ischemic brain through inhibition of microglial proliferation and activation by targeting cell cycle proteins including cyclin D1, CDK6, and CDC25A [12, 13]. Given its immunoregulatory function in the central nervous system, we investigated in this study the diagnostic and immunoregulatory potential of miR-424 expression in circulating immune cells during the acute stage of ischemic stroke by detecting the alteration of miR-424 levels in circulating blood (in lymphocytes, neutrophils, and plasma), as well as analyzing the correlation between miR-424 levels and the peripheral inflammatory response in ischemic stroke

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