MicroRNA let-7e Is a Potential Circulating Biomarker of Acute Stage Ischemic Stroke

Abstract

The aim of this study is to determine the expression levels and clinical significance of circulating microRNAs (miRNAs), let-7e and miR-338 at different stages following ischemic stroke (IS). Seventy-two patients with IS at the acute stage were enrolled and monitored at different stages, and 51 healthy volunteers were served as the normal controls. Expression of let-7e and miR-338 in serum and cerebral spinal fluid (CSF) samples was analyzed by real-time quantitative PCR. The relationship between expression levels of let-7e and miR-338, National Institutes of Health Stroke Scale (NIHSS) scores, and the levels of serum CRP was analyzed, respectively. Compared to healthy controls, serum let-7e expression levels were significantly increased, while serum miR-338 expression levels were slightly increased in IS patients. Expression levels of Let-7e in serum varied at different stages in IS patients with the lowest expression in the recover stage and highest expression in the acute stage. However, serum miR-338 expression in IS patients was not significantly different in any stage. Compared to healthy controls and nonacute stages of IS groups, let-7e expression in CSF was markedly upregulated in IS patients at the acute stage. Different from that of let-7e, miR-338 expression in CSF was upregulated in IS patients only at the subacute stage but not in the acute stage. Meanwhile, let-7e, which was not significantly correlated with NIHSS scores (r = 0.29, P > 0.05), was positively correlated with the serum CRP levels (r = 0.67, P = 0.033). There is no significant correlation between the miR-338 expression levels and NIHSS scores or serum CRP levels. Moreover, let-7e, but not miR-338, had a high consistency in expression when tested both in CSF and serum samples. Finally, serum let-7e showed a specificity up to 73.4 % and a sensitivity of 82.8 % in IS patients at the acute stage, whereas serum miR-338 in IS patients showed a specificity up to 53.2 % and a sensitivity of 71.9 % in the acute stage. Expression levels of let-7e in serum may serve as a useful noninvasive circulating biomarker for the acute stage of ischemic stroke.

MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke

“…Circulating miRs mediate intercellular communication [36], and some circulating miRs are correlated with brain miR changes after stroke [37]. Previous studies have reported that knockout of miR-126 induces cardiac dysfunction [38, 39].…”

Elevation of brain-enriched miRNAs in cerebrospinal fluid of patients with acute ischemic stroke

“…Only one study besides ours has focused on miRNAs in CSF of stroke patients. Peng et al [49] analyzed the expression of let-7e and miR-338 in CSF from ischemic stroke patients and found up-regulation of let-7e in a group of patients included 1–7 days after symptom onset ( n  = 11) but they did not include any brain-specific miRNAs in their analysis.…”

Plasma MicroRNA-16 Is a Biomarker for Diagnosis, Stratification, and Prognosis of Hyperacute Cerebral Infarction

“…Numerous miRNAs have been implicated in the pathogenesis of stroke by evidence showing them regulating gene expression at multiple epigenetic levels [7–8]. A number of studies have sought to identify differentially regulated circulating miRNAs in stroke patients and validate them as biomarkers [9–11]. However, the existence of multiple stroke etiologies and classifications has complicated the challenge of finding diagnostic markers at the hyperacute stage that have high sensitivity and specificity.…”