Neuroprotective effects of miR-27a against traumatic brain injury via suppressing FoxO3a-mediated neuronal autophagy

Sun, Liqian; Zhao, Manman; Wang, Yan; Liu, Aihua; Lv, Ming; Li, Youxiang; Yang, Xiaoling; Wu, Zhongxue

doi:10.1016/j.bbrc.2016.12.001

Cited by 72 publications

(48 citation statements)

References 23 publications

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“…In this study, we first validated the down-regulation of miR-27a-3p in the serum of patients with ICH. Previous studies have reported that miR-27a is also down-regulated in other brain diseases, including Huntington's disease and traumatic brain injury; however, its elevation exerts a cerebrally protective effect (17)(18)(19). Down-regulation of miR-27a-3p might be not specific for ICH.…”

Section: Discussionmentioning

confidence: 94%

miR-27a-3p protects against blood–brain barrier disruption and brain injury after intracerebral hemorrhage by targeting endothelial aquaporin-11

Jin

Zhu

et al. 2018

Journal of Biological Chemistry

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Previous studies have reported that miR-27a-3p is down-regulated in the serum of patients with intracerebral hemorrhage (ICH), but the implication of miR-27a-3p down-regulation in post-ICH complications remains elusive. Here we verified miR-27a-3p levels in the serum of ICH patients by real-time PCR and observed that miR-27a-3p is also significantly reduced in the serum of these patients. We then further investigated the effect of miR-27a-3p on post-ICH complications by intraventricular administration of a miR-27a-3p mimic in rats with collagenaseinduced ICH. We found that the hemorrhage markedly reduced miR-27a-3p levels in the hematoma, perihematomal tissue, and serum and that intracerebroventricular administration of the miR-27a-3p mimic alleviated behavioral deficits 24 h after ICH. Moreover, ICH-induced brain edema, vascular leakage, and leukocyte infiltration were also attenuated by this mimic. Of note, miR-27a-3p mimic treatment also inhibited neuronal apoptosis and microglia activation in the perihematomal zone. We further observed that the miR-27a-3p mimic suppressed the up-regulation of aquaporin-11 (AQP11) in the perihematomal area and in rat brain microvascular endothelial cells (BMECs). Moreover, miR-27a-3p down-regulation increased BMEC monolayer permeability and impaired BMEC proliferation and migration. In conclusion, miR-27a-3p down-regulation contributes to brain edema, blood-brain barrier disruption, neuron loss, and neurological deficits following ICH. We conclude that application of exogenous miR-27a-3p may protect against post-ICH complications by targeting AQP11 in the capillary endothelial cells of the brain. This study was supported by a grant from the National Natural Science Foundation of China (81271291). The authors declare that they have no conflicts of interest with the contents of this article. This article contains Fig. S1.

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Section: Discussionmentioning

confidence: 94%

miR-27a-3p protects against blood–brain barrier disruption and brain injury after intracerebral hemorrhage by targeting endothelial aquaporin-11

Jin

Zhu

et al. 2018

Journal of Biological Chemistry

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“…miR-223-3p and miR-27a-3p upregulation in EAE motor neurons correlates with motor neuron degeneration. However, previous studies have described neuroprotective roles for miR-223 and miR-27a in models of stroke and traumatic brain injury (Harraz et al ., 2012; Cai et al ., 2016; Sun et al ., 2017). To test if upregulation of these miRNAs contributes to axon degeneration or compensatory neuroprotection in neurons, we performed overexpression and loss of function experiments in dissociated mouse cortical neurons.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-223 protects neurons from degeneration in Experimental Autoimmune Encephalomyelitis

Morquette

Juźwik

Drake

et al. 2018

Preprint

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Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and neurodegeneration in the brain, spinal cord and optic nerve. Neuronal degeneration and death underlie progressive forms of MS and cognitive dysfunction. Neuronal damage is triggered by numerous harmful factors in the brain that engage diverse signalling cascades in neurons thus therapeutic approaches to protect neurons will need to focus on agents that can target broad biological processes. To target the broad spectrum of signaling events that mediate neurodegeneration in MS we have focused on non-coding small microRNAs (miRNAs). microRNAs are epigenetic regulators of protein expression, targeting messenger RNAs (mRNAs) and inhibiting their translation. Dysregulation of miRNAs has been described in many neurodegenerative diseases including MS. In this study we identified two miRNAs, miR-223-3p and miR-27a-3p, that were upregulated in neurons in the experimental autoimmune encephalomyelitis (EAE) mouse model of CNS inflammation and in active MS lesions. Overexpression of miR-27a-3p or miR-223-3p protected dissociated cortical neurons from degeneration in response to peripheral blood mononuclear cell conditioned media (PBMC-CM). Introduction of miR-223-3p in vivo in mouse retinal ganglion cells (RGCs) protected RGC axons from degeneration in the EAE model. By in silico analysis we found that mRNAs in the glutamate receptor (GluR) pathway are enriched in miR-27a-3p and miR-223-3p targets. Antagonism of the GluR pathway protected neurons from PBMC-CM-dependent degeneration. Our results suggest that miR-223-3p and miR-27a-3p are upregulated in response to inflammation to mediate a compensatory neuroprotective gene expression program that desensitizes neurons to glutamate by downregulating mRNAs involved in GluR signalling.

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“…LncRNAs are larger than 200 nucleotides, and their importance in gene expression, key cellular processes, metastasis and disease prognosis in cancer has been largely studied [6,7], including in glioma [8,9]. miRNAs are 20-25 nucleotides in length, and they down-regulate gene expression by binding with target mRNAs post-transcriptionally thus resulting in transcript degradation [10]. miRNAs exert critical functions in fundamental cellular process such as cell proliferation, apoptosis, development and inflammation [11].…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA NCK1-AS1 promotes the tumorigenesis of glioma through sponging microRNA-138-2-3p and activating the TRIM24/Wnt/β-catenin axis

Huang

et al. 2020

J Exp Clin Cancer Res

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Background: Glioma is a common brain malignancy with high mortality. The competing endogenous RNA (ceRNA) networks may play key roles in cancer progression. This study was conducted to probe the role of long noncoding RNA (lncRNA) NCK1-AS1 in glioma progression and the involved mechanisms.Methods: Microarray analyses were performed to explore the lncRNAs/miRNAs/genes with differential expression in glioma. NCK1-AS1 levels in glioma tissues and normal brain tissues, and in glioma cell lines and normal human glial cells were identified. The interactions among NCK1-AS1, miR-138-2-3p and TRIM24 were validated through luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Gain-and loss-of functions of NCK1-AS1, miR-138-2-3p and TRIM24 were performed to identify their roles in the behaviors of glioma cells. The activity of the Wnt/β-catenin pathway was measured. In vivo experiments were performed as well.Results: High expression of NCK1-AS1 was found in glioma tissues and cells, especially in U251 cells. Online predictions and the integrated experiments identified that NCK1-AS1 elevated the TRIM24 expression through sponging miR-138-2-3p, and further activated the Wnt/β-catenin pathway. Artificial silencing of NCK1-AS1 or upregulation of miR-138-2-3p led to inhibited proliferation, invasion and migration but promoted cell apoptosis of U251 cells, while up-regulation of TRIM24 reversed these changes, and it activated the Wnt/β-catenin pathway. The in vitro results were reproduced in in vivo experiments.Conclusions: Our study suggested that NCK1-AS1 might elevate TRIM24 expression and further activate the Wnt/βcatenin pathway via acting as a ceRNA for miR-138-2-3p. Silencing of NCK1-AS1 might inhibit the progression of glioma.

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Neuroprotective effects of miR-27a against traumatic brain injury via suppressing FoxO3a-mediated neuronal autophagy

Cited by 72 publications

References 23 publications

miR-27a-3p protects against blood–brain barrier disruption and brain injury after intracerebral hemorrhage by targeting endothelial aquaporin-11

miR-27a-3p protects against blood–brain barrier disruption and brain injury after intracerebral hemorrhage by targeting endothelial aquaporin-11

MicroRNA-223 protects neurons from degeneration in Experimental Autoimmune Encephalomyelitis

Long non-coding RNA NCK1-AS1 promotes the tumorigenesis of glioma through sponging microRNA-138-2-3p and activating the TRIM24/Wnt/β-catenin axis

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