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

Peng, Guoping; Yuan, Yuan; Wu, Shanshan; He, Fangping; Hu, Yewen; Luo, Benyan

doi:10.1007/s12975-015-0422-x

Cited by 59 publications

(34 citation statements)

References 36 publications

(42 reference statements)

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“…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].…”

Section: Discussionmentioning

confidence: 99%

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

Chen

Cui

Yang

et al. 2017

Transl. Stroke Res.

126

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Cardiovascular diseases are approximately three times higher in patients with neurological deficits than in patients without neurological deficits. MicroRNA-126 (MiR-126) facilitates vascular remodeling and decreases fibrosis and is emerging as an important factor in the pathogenesis of cardiovascular diseases and cerebral stroke. In this study, we tested the hypothesis that decreased miR-126 after ischemic stroke may play an important role in regulating cardiac function. Wild-type (WT), specific conditional-knockout endothelial cell miR-126 (miR-126EC−/−), and miR-126 knockout control (miR-126fl/fl) mice were subjected to distal middle cerebral artery occlusion (dMCAo) (n = 10/group). Cardiac hemodynamics and function were measured using transthoracic Doppler echocardiography. Mice were sacrificed at 28 days after dMCAo. WT mice subjected to stroke exhibited significantly decreased cardiac ejection fraction and increased myocyte hypertrophy, fibrosis as well as increased heart inflammation, infiltrating macrophages, and oxidative stress compared to non-stroke animals. Stroke significantly decreased serum and heart miR-126 expression and increased miR-126 target genes, vascular cell adhesion protein-1, and monocyte chemotactic protein-1 gene, and protein expression in the heart compared to non-stroke mice. MiR-126EC−/− mice exhibited significantly decreased cardiac function and increased cardiomyocyte hypertrophy, fibrosis, and inflammatory factor expression after stroke compared to miR-126fl/fl stroke mice. Exosomes derived from endothelial cells of miR-126EC−/− (miR-126EC−/−EC-Exo) mice exhibited significantly decreased miR-126 expression than exosomes derived from miR-126fl/fl (miR-126fl/fl-EC-Exo) mice. Treatment of cardiomyocytes subjected to oxygen glucose deprivation with miR-126fl/fl-EC-Exo exhibited significantly decreased hypertrophy than with miR-126EC−/−EC-Exo treatment. Ischemic stroke directly induces cardiac dysfunction. Decreasing miR-126 expression may contribute to cardiac dysfunction after stroke in mice.

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Section: Discussionmentioning

confidence: 99%

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

Chen

Cui

Yang

et al. 2017

Transl. Stroke Res.

126

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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BackgroundThe purpose of this study was to investigate the potential of cerebrospinal fluid miRNAs as diagnostic biomarkers of acute ischemic stroke using three different profiling techniques in order to identify and bypass any influence from technical variation.MethodsCerebrospinal fluid (CSF) from patients with acute ischemic stroke (n = 21) and controls (n = 21) was collected by lumbar puncture. miRNA analysis was performed with three different methods: 1) Trizol RNA extraction followed by Illumina Next Generation Sequencing (NGS) on all small RNAs, 2) Exiqon RNA extraction protocol and miRNA qPCR assays, and 3) validation of 24 selected miRNAs with Norgen Biotek RNA extraction protocol and Applied Biosystems qPCR assays.ResultsNGS detected 71 frequently expressed miRNAs in CSF of which brain-enriched miR-9-5p and miR-128-3p were significantly higher in CSF of stroke patients compared to controls. When dividing stroke patients into groups according to infarct size several brain-enriched miRNAs (miR-9-5p, miR-9-3p, miR-124-3p, and miR-128-3p) were elevated in patients with infarcts >2 cm3. This trend appeared in data from both NGS, qPCR (Exiqon), and qPCR (Applied Biosystems) but was only statistically significant in some of the measurement platforms.ConclusionsSeveral brain-enriched miRNAs are elevated in the CSF three days after stroke onset, suggesting that these miRNAs reflect the brain damage caused by ischemia. The expression differences seem, however, limited to patients with larger ischemic brain injury, which argues against the use of CSF miRNAs as diagnostic biomarkers of stroke based on current methods.Electronic supplementary materialThe online version of this article (doi:10.1186/s40364-017-0104-9) contains supplementary material, which is available to authorized users.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Tian

Yang

et al. 2016

PLoS ONE

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Indices for the diagnosis of hyperacute cerebral infarction (HACI) and the prediction of prognosis are essential for timely and appropriate management. MicroRNAs (miRNAs) that regulate gene expression following stroke have potential use as prognostic markers of HACI. Here, we explored whether concentrations of circulating miRNAs correlate with clinical outcomes and thus form a system of stroke stratification. Plasma samples from patients with HACI (n = 7) and age-matched healthy volunteers (HVT, n = 4) were screened by microarray to find differentially expressed miRNAs, some of which were further verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (HACI:HVT = 33:23). The target genes of the miRNAs with verified differential expression were investigated by GO and KEEG analyses. Using the TOAST (OCSP) criteria and the 3-month modified Rankin Score (mRS), relationships among the expression patterns of specific miRNAs, stroke stratification, and clinical prognosis were determined. The microarray analysis revealed 12 differentially expressed miRNAs. Among seven selected miRNAs verified with qRT-PCR, miR-16 expression in the HACI group was the most significantly different from the HVT group (P < 0.01). Bioinformatics analysis showed that the potential target genes of miR-16 were mainly involved in programmed cell death and the p53 signaling pathways. Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of miR-16 was 0.775 (sensitivity 69.7% and specificity 87%) and 0.952 (sensitivity 100% and specificity 91.3%) in overall patients and patients with large artery atherosclerosis (LAAS), respectively. Elevated miR-16 expression was associated with the stroke subtype of LAAS, total anterior circulation infarction, partial anterior circulation infarction, and poor prognosis (P < 0.05). A diagnostic method based on rapid measurement of plasma miR-16 has the potential to identify hyperacute cerebral infarction with LAAS with high sensitivity and specificity, which would inform and improve early treatment decisions and disease management.

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

Cited by 59 publications

References 36 publications

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

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

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

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

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