Dysregulation of long non-coding RNAs in mouse models of localization-related epilepsy

Lee, Doo Young; Moon, Jangsup; Lee, Sang Kun; Jung, Keun‐Hwa; Park, Dong-Kyu; Yoo, Jung-Seok; Sunwoo, Jun Sang; Byun, Jung-Ick; Lim, Jong-Deock; Kim, Tae‐Joon; Jung, Ki-Young; Kim, Manho; Jeon, Daejong; Chu, Kon

doi:10.1016/j.bbrc.2015.04.149

Cited by 59 publications

(44 citation statements)

References 31 publications

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“…However, they are gaining interest within the scientific and medical community [63] owing to their potential involvement in disease [88, 89]. Experiments in mouse models have demonstrated that dysregulation of certain lncRNAs could be associated with epilepsy [90], and a role in gene regulation is proposed for the vast number of unstudied cases [91], which makes them interesting candidates for new targeted therapies and disease diagnostics [92]. For example, experiments in a knock-in mouse model of Dravet syndrome have shown that the upregulation of the healthy allele of SCN1A by targeting a lncRNA improved the seizure phenotype [93].…”

Section: Classifying Genes and Other Genomic Elementsmentioning

confidence: 99%

Genome annotation for clinical genomic diagnostics: strengths and weaknesses

et al. 2017

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The Human Genome Project and advances in DNA sequencing technologies have revolutionized the identification of genetic disorders through the use of clinical exome sequencing. However, in a considerable number of patients, the genetic basis remains unclear. As clinicians begin to consider whole-genome sequencing, an understanding of the processes and tools involved and the factors to consider in the annotation of the structure and function of genomic elements that might influence variant identification is crucial. Here, we discuss and illustrate the strengths and weaknesses of approaches for the annotation and classification of important elements of protein-coding genes, other genomic elements such as pseudogenes and the non-coding genome, comparative-genomic approaches for inferring gene function, and new technologies for aiding genome annotation, as a practical guide for clinicians when considering pathogenic sequence variation. Complete and accurate annotation of structure and function of genome features has the potential to reduce both false-negative (from missing annotation) and false-positive (from incorrect annotation) errors in causal variant identification in exome and genome sequences. Re-analysis of unsolved cases will be necessary as newer technology improves genome annotation, potentially improving the rate of diagnosis.

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Section: Classifying Genes and Other Genomic Elementsmentioning

confidence: 99%

Genome annotation for clinical genomic diagnostics: strengths and weaknesses

et al. 2017

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“…LncRNAs have been shown to be abundantly expressed in central neuron system (CNS) and play important roles in the development and disease of CNS (Mercer et al, 2008;Ng et al, 2013), including epilepsy (Lee et al, 2015), multiple sclerosis (Zhang et al, 2017), and ischemic stroke (Bhattarai et al, 2017). Moreover, lncRNAs were reported to be involved in the pathogenesis of neurodegenerative disease, including Alzheimer's disease (AD), Huntington disease, and PD.…”

Section: Introductionmentioning

confidence: 99%

Dysregulated Long Non-coding RNAs in Parkinson’s Disease Contribute to the Apoptosis of Human Neuroblastoma Cells

Fan

Yang

et al. 2019

Front. Neurosci.

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The molecular mechanism underlying Parkinson's disease (PD), an increasingly common neurodegenerative disease, remains unclear. Long non-coding RNA (lncRNA) plays essential roles in gene expression and human diseases. We hypothesize that lncRNAs are involved in neuronal degeneration of PD. Using microarray, we identified 122 differentially expressed (DE) lncRNAs and 48 DE mRNAs between the circulating leukocytes from PD patients and healthy controls. There were 714 significant correlations (r ≥ 0.8 or ≤−0.8, p < 0.05) among the DE lncRNAs and mRNAs. Gene function and pathway analysis of the 48 DE mRNAs revealed biological pathways related to PD pathogenesis, including immune response, inflammatory response, MAPK, and Jak-STAT pathway. In a cohort of 72 PD patients and 22 healthy controls, the upregulation of four lncRNAs (AC131056.3-001, HOTAIRM1, lnc-MOK-6:1, and RF01976.1-201) in circulating leukocytes of PD patients were further confirmed. These lncRNAs were also upregulated in THP-1 cells, a human monocytic cell line, after inflammatory stimulation. Interestingly, the conditioned culture medium of THP-1 cells or 6-OHDA significantly increased the expression of these lncRNAs in SH-SY5Y cells, a human neuroblastoma cell line expressing dopaminergic markers. Importantly, overexpression of AC131056.3-001 or HOTAIRM1 increased baseline and 6-OHDAinduced apoptosis of SH-SY5Y cells. Taken together, we identified distinct expression profiles of lncRNA and mRNA in circulating leukocytes between PD patients and healthy controls. Dysregulated lncRNAs such as HOTAIRM1 and AC131056.3-001 may contribute to PD pathogenesis by promoting the apoptosis of dopaminergic neuron.

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“…Studies had shown that Aβ induced neurotoxicity similar to the pathology of AD, and was widely used to construct AD model in vitro [17]. It was reported that lncRNAs were associated with neurological diseases, such as neurodegenerative disorder and epilepsy [18,19]. Studies had revealed that the hyper-phosphorylation of Tau leads to the formation of neurofibrillary tangles, which is highly related to the neurodegenerative changes in AD [20,21].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of long non-coding RNA SOX21-AS1 attenuates amyloid-β-induced neuronal damage by sponging miR-107

Fan

et al. 2020

Bioscience Reports

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Correspondence: Ling Han (shuixiebu997@126.com) Background: Alzheimer's disease (AD), which has no effective drugs to delay or prevent its progression, is a multifactorial complex neurodegenerative disease. Long non-coding RNA SOX21 antisense RNA1 (SOX21-AS1) is associated with the development of AD, but the underlying molecular mechanism of SOX21-AS1 in AD is still largely unclear. Methods: To construct the AD model, SH-SY5Y and SK-N-SH cells were treated with amyloid-β 1-42 (Aβ 1-42 ). Quantitative real-time polymerase chain reaction (qRT-PCR) was executed to detect the expression of SOX21-AS1 and miRNA-107. Western blot analysis was utilized to assess the levels of phosphorylated Tau (p-Tau). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) or flow cytometry assay was employed to determine the viability and apoptosis of SH-SY5Y and SK-N-SH cells. The relationship between SOX21-AS1 and miRNA-107 was verified with the dual-luciferase reporter assay. Results: SOX21-AS1 expression was augmented while miR-107 expression was decreased in Aβ 1-42 -treated SH-SY5Y and SK-N-SH cells. Moreover, Aβ 1-42 elevated the levels of p-Tau and impeded viability and induced apoptosis of SH-SY5Y and SK-N-SH cells. Also, SOX21-AS1 silencing attenuated Aβ 1-42 mediated the levels of p-Tau, viability, and apoptosis of SH-SY5Y and SK-N-SH cells. Importantly, SOX21-AS1 acted as a sponge for miR-107 in SH-SY5Y and SK-N-SH cells. Furthermore, the increase in p-Tau levels and apoptosis and the repression of viability of Aβ 1-42 -treated SH-SY5Y and SK-N-SH cells mediated by miR-107 inhibition were partly recovered by SOX21-AS1 depletion. Conclusion: SOX21-AS1 silencing could attenuate Aβ 1-42 -induced neuronal damage by sponging miR-107, which provided a possible strategy for the treatment of AD.

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Dysregulation of long non-coding RNAs in mouse models of localization-related epilepsy

Cited by 59 publications

References 31 publications

Genome annotation for clinical genomic diagnostics: strengths and weaknesses

Genome annotation for clinical genomic diagnostics: strengths and weaknesses

Dysregulated Long Non-coding RNAs in Parkinson’s Disease Contribute to the Apoptosis of Human Neuroblastoma Cells

Knockdown of long non-coding RNA SOX21-AS1 attenuates amyloid-β-induced neuronal damage by sponging miR-107

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