Integrative analysis of expression profile indicates the ECM receptor and LTP dysfunction in the glioma-related epilepsy

Wang, Zhi-Bin; Qu, Jian; Xie, Ping; Yang, Zhiquan; Mao, Chen-Xue; Zhang, Ying; He, Zhengwen; Yang, Zhiyong; Mao, Xiao‐Yuan; Liu, Zhao‐Qian

doi:10.1186/s12864-022-08665-8

Cited by 5 publications

(3 citation statements)

References 52 publications

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“…miR-10b-5p suppressed the calcium signaling pathway and LTP. The up-regulation of miR-10b-5p in the hippocampus reduced the BDNF level and caused cognition impairment in mice [ 73 , 74 ]. In addition, miR-10b-5p has been observed to facilitate the differentiation of striatal neurons and be associated with Huntington’s disease [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

Whole-Transcriptome Analysis of Repeated Low-Level Sarin-Exposed Rat Hippocampus and Identification of Cerna Networks to Investigate the Mechanism of Sarin-Induced Cognitive Impairment

Shi

Liu

Jin

et al. 2023

Biology

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Sarin is a potent organophosphorus nerve agent that causes cognitive dysfunction, but its underlying molecular mechanisms are poorly understood. In this study, a rat model of repeated low-level sarin exposure was established using the subcutaneous injection of 0.4 × LD50 for 21 consecutive days. Sarin-exposed rats showed persistent learning and memory impairment and reduced hippocampal dendritic spine density. A whole-transcriptome analysis was applied to study the mechanism of sarin-induced cognitive impairment, and a total of 1035 differentially expressed mRNA (DEmRNA), including 44 DEmiRNA, 305 DElncRNA, and 412 DEcircRNA, were found in the hippocampus of sarin-treated rats. According to Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and Protein–Protein Interaction (PPI) analysis, these DERNAs were mainly involved in neuronal synaptic plasticity and were related to the pathogenesis of neurodegenerative diseases. The circRNA/lncRNA–miRNA–mRNA ceRNA network was constructed, in which Circ_Fmn1, miR-741-3p, miR-764-3p, miR-871-3p, KIF1A, PTPN11, SYN1, and MT-CO3 formed one circuit, and Circ_Cacna1c, miR-10b-5p, miR-18a-5p, CACNA1C, PRKCD, and RASGRP1 constituted another circuit. The balance between the two circuits was crucial for maintaining synaptic plasticity and may be the regulatory mechanism by which sarin causes cognitive impairment. Our study reveals the ceRNA regulation mechanism of sarin exposure for the first time and provides new insights into the molecular mechanisms of other organophosphorus toxicants.

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Section: Discussionmentioning

confidence: 99%

Whole-Transcriptome Analysis of Repeated Low-Level Sarin-Exposed Rat Hippocampus and Identification of Cerna Networks to Investigate the Mechanism of Sarin-Induced Cognitive Impairment

Shi

Liu

Jin

et al. 2023

Biology

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“…In the last decade, calcium signaling has been widely accepted as an important factor in epileptogenesis [16]. Therefore, the down-regulation of miR-10a-5p may contribute to the activation of calcium signaling [5]. Furthermore, in a temporal lobe epilepsy-induced model, an antiepileptic phenotype was observed if miR-10a-5p was inhibited, and combined inhibition with miR-21a-5p and miR-142a-5p reduced spontaneous seizures in epileptic mice [6].…”

Section: Discussionmentioning

confidence: 99%

“…The expression of miR-146a is elevated in the brain tissue of epileptic mice and negatively regulates the KLF4 gene in epileptic cell models to affect synaptic plasticity [4]. Differential expression of miR-10a has been detected in brain tissues of glioma-induced epilepsy patients, suggesting an important role of miR-10a in mediating neural disorders [5]. In animal models of temporal lobe epilepsy, a therapeutic effect is observed after the knockdown of miR-10a-5p, miR-21a-5p and miR-142a-5p [6].…”

Section: Introductionmentioning

confidence: 99%

miR-10a induces inflammatory responses in epileptic hippocampal neurons of rats via PI3K/Akt/mTOR signaling pathway

Lu¹,

Wang²,

Ma³

et al. 2023

NeuroReport

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Epilepsy is a common chronic neurological disorder worldwide. MicroRNAs (miRNAs) play an important role in the pathogenesis of epilepsy. However, the mechanism of the regulatory effect of miR-10a on epilepsy is unclear. In this study, we investigated the effect of miR-10a expression on the PI3K/Akt/mTOR signaling pathway and inflammatory cytokines in epileptic hippocampal neurons of rats. The miRNA differential expression profile of rat epileptic brain was analyzed using bioinformatic approaches. Neonatal Sprague–Dawley rat hippocampal neurons were prepared as epileptic neuron models in vitro by replacing culture medium with magnesium-free extracellular solution. The hippocampal neurons were transfected with miR-10a mimics, and transcript levels of miR-10a, PI3K, Akt and mTOR were detected by quantitative reverse transcription-PCR, and PI3K, mTOR, Akt, TNF-α, IL-1β, IL-6 protein expression levels were detected by Western blot. Cytokines secretory levels were detected by ELISA. Sixty up-regulated miRNAs were identified in the hippocampal tissue of epileptic rats and might affect the PI3K-Akt signaling pathway. In the epileptic hippocampal neurons model, the expression levels of miR-10a were significantly increased, with decreasing levels of PI3K, Akt and mTOR, and increasing levels of TNF-α, IL-1β and IL-6. The miR-10a mimics promoted the expression of TNF-α, IL-1β and IL-6. Meanwhile, miR-10a inhibitor activated PI3K/Akt/mTOR pathway and inhibited cytokines secretion. Finally, cytokine secretion was increased by treated with PI3K inhibitor and miR-10a inhibitor. The miR-10a may promote inflammatory responses in rat hippocampal neurons by inhibiting the PI3K/Akt/mTOR pathway, suggesting that miR-10a may be one of the target therapeutic molecules for epilepsy treatment.

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LINC00894 Regulates Cerebral Ischemia/Reperfusion Injury by Stabilizing EIF5 and Facilitating ATF4-Mediated Induction of FGF21 and ACOD1 Expression

Chen,

Cui,

Han

et al. 2024

Neurochem Res

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The non-coding RNA LINC00894 modulates tumor proliferation and drug resistance. However, its role in brain is still unclear. Using RNA-pull down combined with mass spectrometry and RNA binding protein immunoprecipitation, EIF5 was identified to interact with LINC00894. Furthermore, LINC00894 knockdown decreased EIF5 protein expression, whereas LINC00894 overexpression increased EIF5 protein expression in SH-SY5Y and BE(2)-M17 (M17) neuroblastoma cells. Additionally, LINC00894 affected the ubiquitination modification of EIF5. Adeno-associated virus (AAV) mediated LINC00894 overexpression in the brain inhibited the expression of activated Caspase-3, while increased EIF5 protein level in rats and mice subjected to transient middle cerebral artery occlusion reperfusion (MCAO/R). Meanwhile, LINC00894 knockdown increased the number of apoptotic cells and expression of activated Caspase-3, and its overexpression decreased them in the oxygen–glucose deprivation and reoxygenation (OGD/R) in vitro models. Further, LINC00894 was revealed to regulated ATF4 protein expression in condition of OGD/R and normoxia. LINC00894 knockdown also decreased the expression of glutamate-cysteine ligase catalytic subunit (GCLC) and ATF4, downregulated glutathione (GSH), and the ratio of GSH to oxidized GSH (GSH: GSSG) in vitro. By using RNA-seq combined with qRT-PCR and immunoblot, we identified that fibroblast growth factor 21 (FGF21) and aconitate decarboxylase 1 (ACOD1), as the ATF4 target genes were regulated by LINC00894 in the MCAO/R model. Finally, we revealed that ATF4 transcriptionally regulated FGF21 and ACOD1 expression; ectopic overexpression of FGF21 or ACOD1 in LINC00894 knockdown cells decreased activated Caspase-3 expression in the OGD/R model. Our results demonstrated that LINC00894 regulated cerebral ischemia injury by stabilizing EIF5 and facilitating EIF5-ATF4-dependent induction of FGF21 and ACOD1.

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Integrative analysis of expression profile indicates the ECM receptor and LTP dysfunction in the glioma-related epilepsy

Cited by 5 publications

References 52 publications

Whole-Transcriptome Analysis of Repeated Low-Level Sarin-Exposed Rat Hippocampus and Identification of Cerna Networks to Investigate the Mechanism of Sarin-Induced Cognitive Impairment

Whole-Transcriptome Analysis of Repeated Low-Level Sarin-Exposed Rat Hippocampus and Identification of Cerna Networks to Investigate the Mechanism of Sarin-Induced Cognitive Impairment

miR-10a induces inflammatory responses in epileptic hippocampal neurons of rats via PI3K/Akt/mTOR signaling pathway

LINC00894 Regulates Cerebral Ischemia/Reperfusion Injury by Stabilizing EIF5 and Facilitating ATF4-Mediated Induction of FGF21 and ACOD1 Expression

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