LncRNA GAS5 promotes epilepsy progression through the epigenetic repression of miR-219, in turn affecting CaMKIIγ/NMDAR pathway

Zhao, Chen-Sheng; Liu, Dong-Xing; Fan, Yan-Huai; Wu, Jian-Kun

doi:10.1080/01677063.2022.2067536

Cited by 6 publications

(4 citation statements)

References 45 publications

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“…LncRNAs can affect pathophysiology of epilepsy through different mechanisms among them is regulation of immune responses ( Zhao et al, 2022 ). Tregs have fundamental roles in the regulation of immune activity and are involved in the suppression of epileptogenesis ( Xu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Assessment of Treg-related lncRNAs in epilepsy

Sharifi

Eghtedarian²,

Taheri³

et al. 2023

Front. Mol. Neurosci.

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Recent studies have shown dysregulation of several groups of long non-coding RNAs in the context of epilepsy. According to evidence regarding the role of regulatory T cells in this disorder, we examined expression levels of regulatory T cell-related lncRNAs, namely TH2-LCR, RMRP, IFNG-AS1 (NEST), MAFTRR and FLICR in the blood of epileptic cases compared with controls. Expression of RMRP was lower in patients with refractory epilepsy compared with controls [expression ratio (95% CI) = 0.32 (0.13–0.8), adjusted p-value = 0.0008]. Besides, its expression was lower in refractory patients vs. non-refractory patients [expression ratio (95% CI) = 0.2 (0.1–0.41), adjusted p-value < 0.0001]. Expression of TH2-LCR was lower in refractory patients vs. controls [expression ratio (95% CI) = 0.4 (0.17–0.93), adjusted p-value = 0.0044] and in refractory patients vs. non-refractory ones [Expression ratio = 0.28 (0.19–0.58), p-value < 0.0001]. Expression of NEST was higher in total patients [expression ratio (95% CI) = 2.48 (1.15–5.27), adjusted p-value = 0.0012] and in both groups of patients compared with controls. However, its expression was not different between refractory and non-refractory cases. Similarly, FLICR and MAFTRR were over-expressed in total cases and both groups of patients compared with controls, but their expressions were similar between refractory and non-refractory cases. MAFTRR could differentiate between total epileptic cases and controls with AUC value of 0.8. This lncRNA could separate refractory and non-refractory cases from healthy controls with AUC values of 0.73 and 0.88, respectively. This study provides evidence for deregulation of regulatory T cell-related lncRNAs in epilepsy and their potential role as diagnostic markers in this condition.

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Section: Discussionmentioning

confidence: 99%

Assessment of Treg-related lncRNAs in epilepsy

Sharifi

Eghtedarian²,

Taheri³

et al. 2023

Front. Mol. Neurosci.

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“…These conditions are all associated with an increased incidence of nephrolithiasis. In an animal model of magnesium deficiency-induced disease, inflammatory and apoptosis response-related genes were modulated by epigenetic mechanisms [ 96 ]. Therefore, it would be interesting to explore whether magnesium deficiency or low magnesium urinary excretion, in addition to other lifestyle and environmental factors, could cause prolithogenic epigenetic modifications.…”

Section: Food Compoundsmentioning

confidence: 99%

Unravelling the Complex Relationship between Diet and Nephrolithiasis: The Role of Nutrigenomics and Nutrigenetics

et al. 2022

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Nephrolithiasis is an increasingly prevalent condition, especially in high income countries, and is associated with high morbidity. Extraordinary progress in genetics made the identification of genetic forms of nephrolithiasis possible. These genetic diseases are usually rare and do not account for the most common forms of nephrolithiasis that are the result of several factors such as environment, dietary habits, and predisposing genes. This knowledge has shaped what we classify as nephrolithiasis, a condition that is now recognized as systemic. How and to what extent all these factors interact with one another and end in kidney stone formation, growth, and recurrence is not completely understood. Two new research fields have recently been trying to give some answers: nutrigenomics and nutrigenetics. These fields have the aim of understanding the intricate diet/genome interface that influences gene expression regulation mainly through epigenetic mechanisms and results in specific medical conditions such as cancer, metabolic syndrome, and cardiovascular diseases. Epigenetics seems to play a crucial role and could represent the link between environmental factors, that we are constantly exposed to, and risk factors for nephrolithiasis. In this systematic review, we summarize all the available evidence of proven or hypothesized epigenetic mechanisms related to nephrolithiasis.

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“…Long non-coding RNA growth arrest-specific 5 (GAS5) was markedly upregulated in epileptic cell and animal models, together with a down-regulated expression of miR-219. Moreover, GAS5 could epigenetically suppress the transcriptional miR-219 expression, and knockdown of GAS5 could dramatically promote the cell proliferation of epileptic cells and suppress the inflammation and apoptosis processes, which could be reversed by inhibition of miR-219, suggesting a regulation role of LncRNA GAS5 in the inflammatory response of epilepsy via its effect on miR-219 ( Zhao et al, 2022 ). Cai et al (2020) reported an elevated expression of LncRNA ILF3-AS1 in the serum and hippocampus tissue of epilepsy patients, which promoted the abnormal activation of astrocytes by specifically targeting at miR-212 and up-regulating the expression of inflammatory molecular such as tumor necrosis factor-α (TNF-α), IL-1β, and IL-6.…”

Section: Role Of Long Non-coding Rnas In the Progress Of Epilepsy And...mentioning

confidence: 99%

“…Apart from abrogating the activation of astrocyte, over-expression of LncRNA UCA1 could suppresses the expression of astrocyte glutamate aspartate transporter (GLAST) via JAK/STAT signaling pathway, result in a reduced frequency of the of epilepsy seizures and a promotion of learning and memory in temporal lobe epilepsy rats ( Wang et al, 2020 ). Besides, the regulation effect of LncRNA GAS5 in epilepsy was also involved in the regulation of Calmodulin-dependent protein kinase II (CaMKII)γ/ N -methyl-D-aspartate receptor (NMDAR) pathway ( Zhao et al, 2022 ). Moreover, non-coding RNA-dependent balanced gene regulation in embryonic brain has been reported to be critical for proper formation of GABA-dependent neuronal circuitry in adult brain ( Bond et al, 2009 ).…”

Section: Role Of Long Non-coding Rnas In the Progress Of Epilepsy And...mentioning

confidence: 99%

Long non-coding RNAs: Potential therapeutic targets for epilepsy

Liu¹,

Fan²,

Ma³

et al. 2022

Front. Neurosci.

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Epilepsy is a common and disastrous neurological disorder characterized by abnormal firing of neurons in the brain, affecting about 70 million people worldwide. Long non-coding RNAs (LncRNAs) are a class of RNAs longer than 200 nucleotides without the capacity of protein coding, but they participate in a wide variety of pathophysiological processes. Alternated abundance and diversity of LncRNAs have been found in epilepsy patients and animal or cell models, suggesting a potential role of LncRNAs in epileptogenesis. This review will introduce the structure and function of LncRNAs, summarize the role of LncRNAs in the pathogenesis of epilepsy, especially its linkage with neuroinflammation, apoptosis, and transmitter balance, which will throw light on the molecular mechanism of epileptogenesis, and accelerate the clinical implementation of LncRNAs as a potential therapeutic target for treatment of epilepsy.

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LncRNA GAS5 promotes epilepsy progression through the epigenetic repression of miR-219, in turn affecting CaMKIIγ/NMDAR pathway

Cited by 6 publications

References 45 publications

Assessment of Treg-related lncRNAs in epilepsy

Assessment of Treg-related lncRNAs in epilepsy

Unravelling the Complex Relationship between Diet and Nephrolithiasis: The Role of Nutrigenomics and Nutrigenetics

Long non-coding RNAs: Potential therapeutic targets for epilepsy

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