Long Noncoding RNA FosDT Promotes Ischemic Brain Injury by Interacting with REST-Associated Chromatin-Modifying Proteins

Mehta, Suresh L.; Kim, Tae-Hee; Vemuganti, Raghu

doi:10.1523/jneurosci.2943-15.2015

Cited by 117 publications

(130 citation statements)

References 40 publications

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“…For example, Yan et al reported that the up-regulated lncRNA maternally expressed gene 3 (MEG3) functioned as a cell death promoter in ischemic stroke and physically and functionally interacted with p53 to mediate ischemic neuronal death in stroke [33]. Mehta et al exhibited that lncRNA Fos downstream transcript (FosDT) promoted ischemic brain injury by interacting with REST-associated chromatin-modifying proteinsSin3a and coREST [34]. Wu et al found that lncRNA-N1LR promoted neuroprotection against ischemic stroke by inhibiting p53 phosphorylation and served as a potential target for therapeutic intervention following ischemic brain injury [35].…”

Section: Discussionmentioning

confidence: 99%

Down-Regulation of Lncrna MALAT1 Attenuates Neuronal Cell Death Through Suppressing Beclin1-Dependent Autophagy by Regulating Mir-30a in Cerebral Ischemic Stroke

Guo¹,

Ma²,

Yan³

et al. 2017

Cell Physiol Biochem

155

102

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Background/Aims: LncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was reported to be highly expressed in an in vitro mimic of ischemic stroke conditions. However, the exact biological role of MALAT1 and its underlying mechanism in ischemic stroke remain to be elucidated. Methods: The roles of MALAT1 and miR-30a on cell death and infarct volume and autophagy were evaluated in experimental ischemic stroke. The relationships between miR-30a and MALAT1, Beclin1 were confirmed by luciferase reporter assay. The autophagy inhibitor 3-methyadenine (3-MA) was used to examine the impact of autophagy on ischemic injury. Results: We found that MALAT1, along with the levels of conversion from autophagy-related protein microtubule-associated protein light chain 3-I (LC3-I) to LC3-phosphatidylethanolamine conjugate (LC3-II), as well as Beclin1 were up-regulated and miR-30a was down-regulated in cerebral cortex neurons after oxygen-glucose deprivation (OGD) and mouse brain cortex after middle cerebral artery occlusion-reperfusion (MCAO). Down-regulation of MALAT1 suppressed ischemic injury and autophagy in vitro and in vivo. Furthermore, MALAT1 may serve as a molecular sponge for miR-30a and negatively regulate its expression. In addition, MALAT1 overturned the inhibitory effect of miR-30a on ischemic injury and autophagy in vitro and in vivo, which might be involved in the derepression of Beclin1, a direct target of miR-30a. Mechanistic analyses further revealed that autophagy inhibitor 3-methyadenine (3-MA) markedly suppressed OGD-induced neuronal cell death and MCAO-induced ischemic brain infarction. Conclusion: Taken together, our study first revealed that down-regulation of MALAT1 attenuated neuronal cell death through suppressing Beclin1-dependent autophagy by regulating miR-30a expression in cerebral ischemic stroke. Besides, our study demonstrated a novel lncRNA-miRNA-mRNA regulatory network that is MALAT1-miR-30a-Beclin1 in ischemic stroke, contributing to a better understanding the pathogenesis and progression of ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Down-Regulation of Lncrna MALAT1 Attenuates Neuronal Cell Death Through Suppressing Beclin1-Dependent Autophagy by Regulating Mir-30a in Cerebral Ischemic Stroke

Guo¹,

Ma²,

Yan³

et al. 2017

Cell Physiol Biochem

155

102

View full text Add to dashboard Cite

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“…As we have discussed previously, there are studies which have reported that cerebral miRNA and lncRNAs control epigenetic silencing or activation in mammal also get altered due to cerebral ischemia [27-29]. Moreover, long non-coding RNAs (LncRNAs), also go through changes in the post-stroke brain [30]. MEG3 was the first lncRNA to be found to act as a tumor suppressor and functions its anti-proliferative role through suppression of MDM2 expression with consequent increase of the p53 protein levels in human cancer cells [21, 31].…”

Section: Discussionmentioning

confidence: 99%

Maternally Expressed Gene 3 (MEG3) Enhances PC12 Cell Hypoxia Injury by Targeting MiR-147

Han

Dong

Liu

et al. 2017

Cell Physiol Biochem

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Background/Aims: Cerebral ischemia often leads to breakdown of blood–brain barrier (BBB) and vasogenic edema. It remains to be established whether MEG3 is responsible for the hypoxic damage in neural cells. This study aimed to investigate the role of MEG3 in the hypoxia-induced injuries of PC12 cells. Methods: The PC12 cells were seeded and cultured under hypoxia and normoxia culture conditions. The cell viability determined by trypan blue exclusion, apoptosis using propidium iodide (PI) and fluorescein isothiocynate (FITC)-conjugated Annexin V staining, cell-migration using a modified two-chamber migration assay with a pore size of 8 µM and invasion using 24-well Millicell Hanging Cell Culture inserts with 8 µM PET membranes. Results: Cell viability, relative migration and relative invasion decreased significantly in PC12 cells injured due to hypoxia as compared to control cells. An increase in apoptosis was also observed. The expression of MEG3 was up-regulated in hypoxia-injured PC12 cells. MEG3 overexpression enhanced hypoxia injuries, while MEG3 suppression attenuated the injuries. Meanwhile, MEG3 negatively regulated miR-147 expression. In addition, we found that the expression of Sox2 was increased in PC12 cells after hypoxia and miR-147 negatively regulated Sox2 expression through targets its 3’-UTR. Interesting, Sox2 activated NF-κB pathway and Wnt/β-catenin pathway in PC12 cells. Conclusion: Considering the observations in our study, we can conclude that MEG3 aggravated the hypoxial injury in PC12 cells by down-regulating miR-147 gene and miR-147 further negatively regulated Sox2 expression.

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“…Our data were indirectly supported by other findings. Mehta et al found that FosDT, another lncRNA, promoted neuron death under ischemic conditions while knockdown of FosDT significantly ameliorated ischemic injury in vivo[21]. Liu et al found that UCA1 contributed to cardiomyocyte apoptosis via regulating p27 expression[22].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of BDNF-AS Provides Neuroprotection for Retinal Ganglion Cells against Ischemic Injury

Zhang

Xie

et al. 2016

PLoS ONE

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Background: Brain-derived neurotrophic factor (BDNF) protects retinal ganglion cells against ischemia in ocular degenerative diseases. We aimed to determine the effect of BDNF-AS on the ischemic injury of retinal ganglion cells. Methods: The levels of BDNF and BDNF-AS were measured in retinal ganglion cells subjected to oxygen and glucose deprivation. The lentiviral vectors were constructed to either overexpress or knock out BDNF-AS. The luciferase reporter gene assay was used to determine whether BDNF-AS could target its seed sequence on BDNF mRNA. The methyl thiazolyl tetrazolium assay was used to determine cell viability, and TUNEL staining was used for cell apoptosis. Results: The levels of BDNF-AS were negatively correlated with BDNF in ischemic retinal ganglion cells. BDNF-AS directly targeted its complementary sequences on BDNF mRNA. BDNF-AS regulated the expression of BDNF and its related genes in retinal ganglion cells. Down-regulation of BDNF-AS increased cell viability and decreased the number of TUNEL-positive retinal ganglion cells under oxygen and glucose deprivation conditions. Conclusion: Inhibition of BDNF-AS protected retinal ganglion cells against ischemia by increasing the levels of BDNF.

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Long Noncoding RNA FosDT Promotes Ischemic Brain Injury by Interacting with REST-Associated Chromatin-Modifying Proteins

Cited by 117 publications

References 40 publications

Down-Regulation of Lncrna MALAT1 Attenuates Neuronal Cell Death Through Suppressing Beclin1-Dependent Autophagy by Regulating Mir-30a in Cerebral Ischemic Stroke

Down-Regulation of Lncrna MALAT1 Attenuates Neuronal Cell Death Through Suppressing Beclin1-Dependent Autophagy by Regulating Mir-30a in Cerebral Ischemic Stroke

Maternally Expressed Gene 3 (MEG3) Enhances PC12 Cell Hypoxia Injury by Targeting MiR-147

Inhibition of BDNF-AS Provides Neuroprotection for Retinal Ganglion Cells against Ischemic Injury

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