Long non-coding RNA H19 contributes to apoptosis of hippocampal neurons by inhibiting let-7b in a rat model of temporal lobe epilepsy

Han, Chunlei; Ge, Ming; Liu, Yunpeng; Zhao, Xuemin; Wang, Kailiang; Chen, Ning; Hu, Wei Shou; Zhang, Jianguo; Li, Liang; Meng, Fangang

doi:10.1038/s41419-018-0496-y

Cited by 87 publications

(83 citation statements)

References 48 publications

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“…To our knowledge, the regulation of apoptotic genes is cell-type dependent. For instance, previous studies demonstrated that the lncRNA H19 inhibited MC apoptosis [51], but promoted apoptosis in cardiomyocytes and hippocampal neurons [52,53]. Hence, given the cell-type speci city of Dex induced responses, the roles and underlying mechanisms of the genes identi ed in the present study need further elucidation.…”

Section: Discussionmentioning

confidence: 81%

Differential Expression Profiles of Long Noncoding RNA and mRNA in Dexamethasone-Induced Apoptosis of Human Bone Marrow Mesenchymal Stem Cells

Wang

et al. 2020

Preprint

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Background Abnormalities in apoptosis, cell cycle, and proliferation of human bone marrow mesenchymal stem cells (hBMSCs) significantly impact bone metabolism and remodeling, and thereby cause various skeletal disorders. Long-term exposure to a high dosage of dexamethasone (Dex) induces apoptosis and inhibits proliferation of mesenchymal stromal cells (MSCs), which are probably the primary causes of osteoporosis (OP) and steroid-induced osteonecrosis of the femoral head (SONFH). However, to date, the exact mechanisms of Dex-induced apoptosis of BMSCs are still poorly defined. Methods A microarray was used to identify differentially expressed lncRNA and mRNA in Dex-induced apoptosis of hBMSCs, and bioinformatics was used to further explore the role of these differentially expressed lncRNAs and mRNAs by the coding and noncoding (CNC) network. Furthermore, validation of the microarray results was performed by quantitative real-time PCR (qRT-PCR) analysis. Results The microarray analysis identified a total of 137 differentially expressed mRNA (90 up-regulated and 47 down-regulated) and 90 differentially expressed lncRNA (61 up-regulated and 29 down-regulated) in Dex-induced apoptosis of hBMSCs. The differentially expressed mRNA and lncRNA were associated with the regulation of cell apoptosis. Meanwhile, several signaling pathways involved in the regulation of cell apoptosis, including mTOR signaling pathway, Ras signaling pathway, HIF-1 signaling pathway, NF-kappa B signaling pathway, and TGF-beta signaling pathway, also were identified in interaction net of the significant pathways (Path-Net) analysis. Furthermore, the CNC network further identified 78 core regulatory genes involved in the regulation of apoptosis. Besides, validation by qRT-PCR of the key differentially expressed mRNA and lncRNA, reported to be closely related to cell apoptosis, confirmed the reliability of the microarray dataset. Conclusions Collectively, we utilized microarray to identify differentially expressed lncRNA and mRNA in Dex-induced apoptotic hBMSCs, and bioinformatics to explore the interaction between the differentially expressed genes. This study demonstrates the molecular mechanisms of Dex-induced apoptosis of hBMSCs and provides a new research direction for the study of the pathogenesis of steroid-induced osteonecrosis of femoral head.

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Section: Discussionmentioning

confidence: 81%

Differential Expression Profiles of Long Noncoding RNA and mRNA in Dexamethasone-Induced Apoptosis of Human Bone Marrow Mesenchymal Stem Cells

Wang

et al. 2020

Preprint

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“…For instance, LncRNA UCA1, which was downregulated in the epileptiform hippocampal neurons and rat of temporal lobe epilepsy, could obstruct seizure-induced brain injury by modulating miR-495 expression [25]. LncRNA H19 was upregulated during the progression of temporal lobe epilepsy and H19 overexpression provoked SE-induced neuronal apoptosis through sponging let-7b [26]. Based on our finding that overexpression of NEAT1 promoted the neuronal apoptosis, we further studied the functional target of NEAT1.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA NEAT1 aggravates epilepsy and seizure-induced neuronal damage by regulating microRNA-139/ROCK1 axis

Hao

Tao

et al. 2020

Preprint

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Background Both long non-coding RNA (lncRNA) NEAT1 and microRNA (miR)-139 are crucial gene regulators in various disorders. This study aims to investigate their role in epilepsy and seizure-induced neuronal damage. Methods In this research, rat model of epilepsy was established by pilocarpine induction. The RNA and protein expression in hippocampal tissues and neurons were determined by RT-qPCR and Western blot analysis, respectively. Microarray analysis was used to predict the relationship between NEAT1 and miR-139 or between miR-139 and ROCK1, and dual luciferase reporter gene assay was performed to verify the interaction. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. The cell apoptosis, levels of inflammatory factors and cell proliferation were detected by flow cytometry, ELISA and EdU assay. Results LncRNA NEAT1 and ROCK1 was upregulated, while the miR-139 was downregulated in hippocampal tissues and neurons of epileptic rats. Overexpression of NEAT1 decreased the activity of neurons, increased cell apoptosis, and increased the level of inflammatory factors. NEAT1 negatively targeted miR-139 to upregulate ROCK1. The RhoA/ROCK1 signaling pathway was activated by NEAT1 overexpression and miR-139 downregulation. Conclusion LncRNA NEAT1 suppressed pilocarpine-induced epilepsy by inhibiting apoptosis of hippocampal neurons through miR-139/RhoA/ROCK1 axis, and thereby inhibiting neuronal injury induced by seizure.

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“…Multiple lncRNAs have been reported to be associated with neuron apoptosis. As the selected examples, lncRNA MALAT1 [22] and lncRNA H19 [23] contributed to the apoptosis of hippocampal neurons. The present work illustrated that silence of MEG3 prevented hypoxia-induced cell viability loss and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Silencing MEG3 protects PC12 cells from hypoxic injury by targeting miR-21

Deng

Liang

2020

Artificial Cells, Nanomedicine, and Biotechnology

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Increasing number of literatures highlighted lncRNA maternally expressed gene 3 (MEG3) as an emerging target for hypoxic-ischaemic brain damage (HIBD). This study attempted to assess the role of MEG3 in a cell model of HIBD. Expression of MEG3 in PC12 cells was suppressed by siRNA-mediated transfection, after which the cells were subjected to hypoxia. Cell viability, apoptosis, migration and the expression of related proteins were assessed. Furthermore, the downstream gene of MEG3 and its downstream signalling pathways were explored. We found that, down-regulation of MEG3 prevented hypoxic injury in PC12 cells, as hypoxia induced viability loss, apoptosis and migration repression were attenuated by transfection with MEG3 siRNA. Meanwhile, MEG3 acted as a miR-21 sponge. The neuroprotective functions of MEG3 silence were flattened when miR-21 was suppressed. Moreover, the deactivation of PI3K/AKT pathway and the activation of NF-jB pathway induced by hypoxia were attenuated by MEG3 silence. As expected, the effects of MEG3 silence on these two signalling were via miR-21. In conclusion, the neuroprotective effects of MEG3 silence on PC12 cells injured by hypoxia were observed in this study. Mechanistically, the neuroprotective effects of MEG3 silence on PC12 cells were via sponging miR-21 and thus regulating PI3K/AKT and NF-jB pathways. HIGHLIGHTS 1. MEG3 is highly expressed in PC12 cells following hypoxic injury; 2. Silence of MEG3 prevents hypoxia-induced cell damage in PC12 cells; 3. MEG3 acts as a miR-21 sponge; 4. MEG3 sponges miR-21 to regulate PI3K/AKT and NF-jB pathways.

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Long non-coding RNA H19 contributes to apoptosis of hippocampal neurons by inhibiting let-7b in a rat model of temporal lobe epilepsy

Cited by 87 publications

References 48 publications

Differential Expression Profiles of Long Noncoding RNA and mRNA in Dexamethasone-Induced Apoptosis of Human Bone Marrow Mesenchymal Stem Cells

Differential Expression Profiles of Long Noncoding RNA and mRNA in Dexamethasone-Induced Apoptosis of Human Bone Marrow Mesenchymal Stem Cells

Long non-coding RNA NEAT1 aggravates epilepsy and seizure-induced neuronal damage by regulating microRNA-139/ROCK1 axis

Silencing MEG3 protects PC12 cells from hypoxic injury by targeting miR-21

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