Date Published: April 1, 2018
Publisher: JKL International LLC
Author(s): Guangwen Li, Qingfeng Ma, Rongliang Wang, Zhibin Fan, Zhen Tao, Ping Liu, Haiping Zhao, Yumin Luo.
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.
Previous studies have suggested that expression of various miRs in circulating blood is rapidly altered after stroke onset, and some specific miRs have the potential to be ischemic stroke biomarkers. 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. We found that elevated miR-424 levels in peripheral immune cells has potential as a diagnostic tool for ischemic stroke, and may have an immunosuppressive effect through inhibiting lymphocyte proliferation by targeting CDK6, resulting in less release of cytokines and neurotrophic factor from lymphocytes and neutrophils, which subsequently affects the severity of acute cerebral infarction.