The Diagnostic Value of Circulating Brain-specific MicroRNAs for Ischemic Stroke

Yang, Zhong‐Bao; Li, Ting-Bo; Zhang, Zhen; Ren, Kai-Di; Zheng, Zhao-Feng; Peng, Jun; Luo, Xiu-Ju

doi:10.2169/internalmedicine.55.5925

Cited by 41 publications

(34 citation statements)

References 32 publications

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“…Yang et al [46] found miR-128b significantly up-regulated in plasma from ischemic stroke patients compared to healthy controls. In addition, miR-124 has previously been associated with ischemic stroke.…”

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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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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“…In particular, the circulating levels of miR-107, miR-128b and miR-153 significantly increase in stroke patients in comparison to healthy volunteers, and their levels positively correlate with the severity of stroke [185]. Moreover, it has recently observed that miR-128 counteracts stress responses mediated by Nrf2 targeting MAFG and, as a consequence, it could mediate the adaptive response during hypoxia both in vitro and in vivo [186].…”

Section: Nrf2 and Mirnas In Ischemic Strokementioning

confidence: 99%

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

Paladino

Conte

Caggiano

et al. 2018

Cell Physiol Biochem

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A general hallmark of neurological diseases is the loss of redox homeostasis that triggers oxidative damages to biomolecules compromising neuronal function. Under physiological conditions the steady-state concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are finely regulated for proper cellular functions. Reduced surveillance of endogenous antioxidant defenses and/or increased ROS/RNS production leads to oxidative stress with consequent alteration of physiological processes. Neuronal cells are particularly susceptible to ROS/RNS due to their biochemical composition. Overwhelming evidences indicate that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-linked pathways are involved in protective mechanisms against oxidative stress by regulating antioxidant and phase II detoxifying genes. As such, Nrf2 deregulation has been linked to both aging and pathogenesis of many human chronic diseases, including neurodegenerative ones such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis. Nrf2 activity is tightly regulated by a fine balance between positive and negative modulators. A better understanding of the regulatory mechanisms underlying Nrf2 activity could help to develop novel therapeutic interventions to prevent, slow down or possibly reverse various pathological states. To this end, microRNAs (miRs) are attractive candidates because they are linked to intracellular redox status being regulated and, post-transcriptionally, regulating key components of ROS/RNS pathways, including Nrf2.

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“…In some studies, expression profiling of blood was conducted in parallel with brain (Liu et al, 2010; Jeyaseelan et al, 2008) and CSF (Sørensen et al, 2014) that showed overlapping patterns of miRNA levels between blood/brain and blood/CSF. The miRNAs that showed altered levels in blood after stroke include miR-107 (Yang et al, 2016b), miR-128b (Yang et al, 2016b), miR-153 (Yang et al, 2016b), miR-124 (Weng et al, 2011; Laterza et al, 2009), miR-210 (Zeng et al, 2011), miR-145 (Gan et al, 2012), miR-21 (Zhou and Zhang, 2014; Tsai et al, 2013), miR-221 (Tsai et al, 2013), miR-30a (Long et al, 2013), miR-126 (Chen et al, 2015a; Long et al, 2013), let-7b (Long et al, 2013), miR-223 (Wang et al, 2014d) and miR-24 (Zhou and Zhang., 2014). Importantly, Yang et al (2014) showed that miR-107 was elevated in the plasma of both rats and humans after stroke.…”

Section: Micrornas As Stroke Biomarkersmentioning

confidence: 99%

Non-coding RNAs and neuroprotection after acute CNS injuries

Chandran

Mehta

2017

Neurochemistry International

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Accumulating evidence indicates that various classes of non-coding RNAs (ncRNAs) including microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs) and long non-coding RNAs (lncRNAs) play important roles in normal state as well as the diseases of the CNS. Interestingly, ncRNAs have been shown to interact with messenger RNA, DNA and proteins, and these interactions could induce epigenetic modifications and control transcription and translation, thereby adding a new layer of genomic regulation. The ncRNA expression profiles are known to be altered after acute CNS injuries including stroke, traumatic brain injury and spinal cord injury that are major contributors of morbidity and mortality worldwide. Hence, a better understanding of the functional significance of ncRNAs following CNS injuries could help in developing potential therapeutic strategies to minimize the neuronal damage in those conditions. The potential of ncRNAs in blood and CSF as biomarkers for diagnosis and/or prognosis of acute CNS injuries has also gained importance in the recent years. This review highlighted the current progress in the understanding of the role of ncRNAs in initiation and progression of secondary neuronal damage and their application as biomarkers after acute CNS injuries.

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The Diagnostic Value of Circulating Brain-specific MicroRNAs for Ischemic Stroke

Cited by 41 publications

References 32 publications

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

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

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

Non-coding RNAs and neuroprotection after acute CNS injuries

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