microRNAs in Stroke Pathogenesis

Tan, Jun; Koo, Yu Xuan; Kaur, Prameet; Liu, F.; Armugam, Arunmozhiarasi; Wong, Poo Sing; Jeyaseelan, Kandiah

doi:10.2174/156652411794859232

Cited by 91 publications

(44 citation statements)

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“…MiRNAs can fit this need as they are known to be released into both blood and CSF and remain stable for days. Hence, many studies evaluated their usefulness as biomarkers for identifying the onset of stroke, TBI and SCI (Reid et al, 2011; Tan et al, 2011; Wang et al, 2013). …”

Section: Micrornas As Potential Biomarkers For Acute Cns Injuriesmentioning

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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Section: Micrornas As Potential Biomarkers For Acute Cns Injuriesmentioning

confidence: 99%

Non-coding RNAs and neuroprotection after acute CNS injuries

Chandran

Mehta

2017

Neurochemistry International

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“…NcRNAs have become a focus in biomedical research in the last half decade and are now regarded as important and essential mediators in major biological/physiological processes impacting development, differentiation, and metabolism, as well as pathologies in a variety of human diseases (Qureshi and Mehler, 2012; Schonrock et al, 2012; Suarez and Sessa, 2009; Taft et al, 2010; Vemuganti, 2013; Wienholds and Plasterk, 2005; Yin et al, 2014). So far in the stroke field, the role of a specific class of small ncRNAs, miRNAs, was mainly investigated in the pathogenesis of stroke (Eacker et al, 2013; Liu et al, 2013; Ouyang et al, 2013; Rink and Khanna, 2010; Saugstad, 2010; Tan et al, 2011; Vemuganti, 2010; Yin et al, 2013b, 2014). Notably, our research team has focused on studying the functional significance of stroke-associated endothelial ncRNAs with a special focus on miRNAs in cerebral endothelial pathophysiology after stroke (Yin et al, 2010a; Yin et al, 2013a; Yin et al, 2013b, 2014; Yin et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Altered long non-coding RNA transcriptomic profiles in brain microvascular endothelium after cerebral ischemia

Zhang

Yuan

Zhang

et al. 2016

Experimental Neurology

185

138

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The brain endothelium is an important therapeutic target for the inhibition of cerebrovascular dysfunction in ischemic stroke. Previously, we documented the important regulatory roles of microRNAs in the cerebral vasculature, in particular the cerebral vascular endothelium. However, the functional significance and molecular mechanisms of other classes of non-coding RNAs in the regulation of cerebrovascular endothelial pathophysiology after stroke are completely unknown. Using RNA sequencing (RNA-seq) technology, we profiled long non-coding RNA (lncRNA) expressional signatures in primary brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation (OGD), an in vitro mimic of ischemic stroke conditions. After 16h of OGD exposure, the expression levels for 362 of the 10,677 lncRNAs analyzed changed significantly, including a total of 147 lncRNAs increased and 70 lncRNAs decreased by more than 2-fold. Among them, the most highly upregulated lncRNAs include Snhg12, Malat1, and lnc-OGD 1006, whereas the most highly downregulated lncRNAs include 281008D09Rik, Peg13, and lnc-OGD 3916. Alteration of the most highly upregulated/downregulated ODG-responsive lncRNAs was further confirmed in cultured BMECs after OGD as well as isolated cerebral microvessels in mice following transient middle cerebral artery occlusion (MCAO) and 24h reperfusion by the quantitative real-time PCR approach. Moreover, promoter analysis of altered ODG-responsive endothelial lncRNA genes by bioinformatics showed substantial transcription factor binding sites on lncRNAs, implying potential transcriptional regulation of those lncRNAs. These findings are the first to identify OGD-responsive brain endothelial lncRNAs, which suggest potential pathological roles for these lncRNAs in mediating endothelial responses to ischemic stimuli. Endothelial-selective lncRNAs may function as a class of novel master regulators in cerebrovascular endothelial pathologies after ischemic stroke.

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“…So far in the stroke field, the role of a specific class of small ncRNAs, miRNAs, was mainly investigated (Rink and Khanna, 2010; Saugstad, 2010; Vemuganti, 2010; Tan et al, 2011; Eacker et al, 2013; Liu et al., 2013; Ouyang et al, 2013; Yin et al, 2013a). Moreover, recent breakthrough microarray profiling studies identifying stroke-responsible alteration of piRNAs (Dharap et al, 2011) and lncRNAs (Dharap et al, 2012; Dharap et al, 2013; Vemuganti, 2013) underscore the importance of other ncRNAs in the pathogenesis of ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

Non-coding RNAs in cerebral endothelial pathophysiology: Emerging roles in stroke

Yin

Hamblin

Chen

2014

Neurochemistry International

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Cerebral vascular endothelial cells form the major element of the blood-brain barrier (BBB) and constitute the primary interface between circulating blood and brain parenchyma. The structural and functional changes in cerebral endothelium during cerebral ischemia are well known to result in BBB disruption, vascular inflammation, edema, and angiogenesis. These complex pathological processes directly contribute to brain infarction, neurological deficits, and post-stroke neurovascular remodeling. Ischemic endothelial dysfunction appears to be tightly controlled by multiple gene signaling networks. Non-coding RNAs (ncRNAs) are functional RNA molecules that are generally not translated into proteins but can actively regulate the expression and function of many thousands of protein-coding genes by different mechanisms. Various classes of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), small nucleolar RNAs (snoRNAs) and piwi-interacting RNAs (piRNAs), are highly expressed in the cerebrovascular endothelium where they serve as critical mediators to maintain normal cerebral vascular functions. Dysregulation of ncRNA activities has been closely linked to the pathophysiology of cerebral vascular endothelium and neurologic functional disorders in the brain’s response to ischemic stimuli. In this review, we summarize recent advancements of these ncRNA mediators in the brain vasculature, highlighting the specific roles of endothelial miRNAs in stroke.

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microRNAs in Stroke Pathogenesis

Cited by 91 publications

References 0 publications

Non-coding RNAs and neuroprotection after acute CNS injuries

Non-coding RNAs and neuroprotection after acute CNS injuries

Altered long non-coding RNA transcriptomic profiles in brain microvascular endothelium after cerebral ischemia

Non-coding RNAs in cerebral endothelial pathophysiology: Emerging roles in stroke

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