The Expression of the Cancer-Associated lncRNA Snhg15 Is Modulated by EphrinA5-Induced Signaling

The Eph receptor tyrosine kinases and their respective ephrin-ligands are an important family of membrane receptors, being involved in developmental processes such as proliferation, migration, and in the formation of brain cancer such as glioma. Intracellular signaling pathways, which are activated by Eph receptor signaling, are well characterized. In contrast, it is unknown so far whether ephrins modulate the expression of lncRNAs, which would enable the transduction of environmental stimuli into our genome through a great gene regulatory spectrum. Applying a combination of functional in vitro assays, RNA sequencing, and qPCR analysis, we found that the proliferation and migration promoting stimulation of mouse cerebellar granule cells (CB) with ephrinA5 diminishes the expression of the cancer-related lncRNA Snhg15. In a human medulloblastoma cell line (DAOY) ephrinA5 stimulation similarly reduced SNHG15 expression. Computational analysis identified triple-helix-mediated DNA-binding sites of Snhg15 in promoters of genes found up-regulated upon ephrinA5 stimulation and known to be involved in tumorigenic processes. Our findings propose a crucial role of Snhg15 downstream of ephrinA5-induced signaling in regulating gene transcription in the nucleus. These findings could be potentially relevant for the regulation of tumorigenic processes in the context of glioma.

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Expression of Eph receptors and their ligands, ephrins, during lipopolysaccharide fever in rats

Physiological Genomics ◽

10.1152/physiolgenomics.00043.2004 ◽

2005 ◽

Vol 21 (2) ◽

pp. 152-160 ◽

Cited By ~ 35

Author(s):

Andrei I. Ivanov ◽

Alexandre A. Steiner ◽

Adrienne C. Scheck ◽

Andrej A. Romanovsky

Keyword(s):

Tyrosine Kinases ◽

Eph Receptors ◽

Phase 2 ◽

Eph Receptor ◽

Cellular Events ◽

Cell Adhesion And Migration ◽

Transcriptional Changes ◽

And Migration

Erythropoietin-producing hepatocellular (Eph) receptor tyrosine kinases and their ligands, ephrins, are involved in embryogenesis and oncogenesis by mediating cell adhesion and migration. Although ephrins can be induced by bacterial LPS in vitro, whether they are involved in inflammation in vivo is unknown. Using differential mRNA display, we found that a febrigenic dose of LPS (50 μg/kg iv) induces a strong transcriptional upregulation of ephrin-A1 in rat liver. We confirmed this finding by real-time RT-PCR. We then quantified the mRNA expression of different ephrins and Eph receptors at phases 1–3 of LPS fever in different organs. Febrile phases 2 (90 min post-LPS) and 3 (300 min) were characterized by robust upregulation (up to 16-fold) and downregulation (up to 21-fold) of several ephrins and Eph receptors. With the exception of EphA2, which showed upregulation in the brain at phase 2, expressional changes of Eph receptors and ephrins were limited to the LPS-processing organs: liver and lung. Characteristic, counter-directed changes in expressional regulation of Eph receptors and their corresponding ligands were found: upregulation of EphA2, downregulation of ephrin-A1 in the liver and lung at phase 2; downregulation of EphB3, upregulation of ephrin-B2 in the liver at phase 2; downregulation of EphA1 and EphA3, upregulation of ephrins-A1 and -A3 in liver at phase 3. In the liver, transcriptional changes of EphA2 and EphB3 at phase 2 were confirmed at protein level. These coordinated, phase-specific responses suggest that different sets of ephrins and Eph receptors may be involved in cellular events (such as disruption of tissue barriers and leukocyte transmigration) underlying different stages of systemic inflammatory response to LPS.

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In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases

Cell ◽

10.1016/0092-8674(95)90425-5 ◽

1995 ◽

Vol 82 (3) ◽

pp. 359-370 ◽

Cited By ~ 557

Author(s):

Uwe Drescher ◽

Claus Kremoser ◽

Claudia Handwerker ◽

Jürgen Löschinger ◽

Masaharu Noda ◽

...

Keyword(s):

Ganglion Cell ◽

Retinal Ganglion Cell ◽

Tyrosine Kinases ◽

Receptor Tyrosine Kinases ◽

Retinal Ganglion ◽

Eph Receptor

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Deferoxamine antioxidant activity on cerebellar granule cells γ-irradiated in vitro

Neurotoxicology and Teratology ◽

10.1016/j.ntt.2004.02.001 ◽

2004 ◽

Vol 26 (3) ◽

pp. 477-483 ◽

Cited By ~ 21

Author(s):

L Guelman

Keyword(s):

Antioxidant Activity ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Cerebellar Granule

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Selective Modulation of Tonic and Phasic Inhibitions in Dentate Gyrus Granule Cells

Journal of Neurophysiology ◽

10.1152/jn.2002.87.5.2624 ◽

2002 ◽

Vol 87 (5) ◽

pp. 2624-2628 ◽

Cited By ~ 325

Author(s):

Zoltan Nusser ◽

Istvan Mody

Keyword(s):

Dentate Gyrus ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Hippocampal Slices ◽

Tonic Inhibition ◽

Adult Rats ◽

Adult Rat ◽

Phasic Inhibition ◽

The Mean

In some nerve cells, activation of GABAA receptors by GABA results in phasic and tonic conductances. Transient activation of synaptic receptors generates phasic inhibition, whereas tonic inhibition originates from GABA acting on extrasynaptic receptors, like in cerebellar granule cells, where it is thought to result from the activation of extrasynaptic GABAA receptors with a specific subunit composition (α6βxδ). Here we show that in adult rat hippocampal slices, extracellular GABA levels are sufficiently high to generate a powerful tonic inhibition in δ subunit–expressing dentate gyrus granule cells. In these cells, the mean tonic current is approximately four times larger than that produced by spontaneous synaptic currents occurring at a frequency of ∼10 Hz. Antagonizing the GABA transporter GAT-1 with NO-711 (2.5 μM) selectively enhanced tonic inhibition by 330% without affecting the phasic component. In contrast, by prolonging the decay of inhibitory postsynaptic currents (IPSCs), the benzodiazepine agonist zolpidem (0.5 μM) augmented phasic inhibition by 66%, while leaving the mean tonic conductance unchanged. These results demonstrate that a tonic GABAA receptor–mediated conductance can be recorded from dentate gyrus granule cells of adult rats in in vitro slice preparations. Furthermore, we have identified distinct pharmacological tools to selectively modify tonic and phasic inhibitions, allowing future studies to investigate their specific roles in neuronal function.

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miR-208a-3p promotes NSCLC proliferation and migration by suppressing lncRNA-MEG3 expression

10.21203/rs.3.rs-877755/v1 ◽

2021 ◽

Author(s):

Linfei Yang ◽

Qian Li ◽

Hai Zhong ◽

Liang Ye ◽

Surong Fang ◽

...

Keyword(s):

Protein Extraction ◽

Underlying Mechanism ◽

In Vitro Assays ◽

Cell Viability Assay ◽

Migration Assay ◽

Normal Tissues ◽

Viability Assay ◽

And Migration ◽

Proliferation And Migration

Abstract Background The disordered expression of maternally expressed gene 3 (MEG3) has been observed in non-small-cell lung cancer (NSCLC). However, the molecular mechanism accounting for this abnormal expression is not fully understood. Methods MEG3 expression was detected by qRT-PCR in 51 cases of NSCLC and adjacent normal tissues. Then, the relationship between MEG3 and miR-208a-3p was assessed in vitro by cell viability assay, cell migration assay, protein extraction and western blot analysis. Resoults We observed that MEG3 expression was decreased in NSCLC tissues. And MEG3 expression was negatively related to lymph node metastasis and differentiation. Moreover, MEG3 expression is regulated by miR-208a-3p expression by overexpression and knockout experiments. Furthermore, we focused on the underlying mechanism of MEG3 downregulation. We found that the overexpression of miR-208a-3p reduced the level of MEG3 expression based on computational predictions and in vitro assays. Using CCK-8 and transwell migration assays, we found that the overexpression of miR-208a-3p can increased proliferation and apoptosis in NSCLC cells. Moreover, the depletion of MEG3 rescued the proliferation and migration induced by miR-208a-3p knockdown. Conclusion Taken together, the results of this study reveal that miR-208a-3p promotes NSCLC tumorigenesis by negatively regulating MEG3 expression and functions as an oncogenic miRNA in NSCLC.

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Tetrabromobisphenol A-induced depolarization of rat cerebellar granule cells: ex vivo and in vitro studies

Chemosphere ◽

10.1016/j.chemosphere.2019.02.032 ◽

2019 ◽

Vol 223 ◽

pp. 64-73 ◽

Cited By ~ 4

Author(s):

Dominik Diamandakis ◽

Elzbieta Zieminska ◽

Marcin Siwiec ◽

Krzysztof Tokarski ◽

Elzbieta Salinska ◽

...

Keyword(s):

Granule Cells ◽

Cerebellar Granule Cells ◽

Ex Vivo ◽

In Vitro Studies ◽

Tetrabromobisphenol A ◽

Cerebellar Granule

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Overexpression of RASAL1 indicates poor prognosis and promotes invasion of ovarian cancer

Open Life Sciences ◽

10.1515/biol-2019-0015 ◽

2019 ◽

Vol 14 (1) ◽

pp. 133-140

Author(s):

Rui-Xia Chang ◽

Ai-Ling Cui ◽

Lu Dong ◽

Su-Ping Guan ◽

Ling-Yan Jiang ◽

...

Keyword(s):

Mitogen Activated Protein Kinase ◽

Cell Counting ◽

In Vitro Assays ◽

Ovarian Adenocarcinoma ◽

Invasion And Migration ◽

Kaplan Meier ◽

Extracellular Signal ◽

Mitogen Activated Protein ◽

And Migration

AbstractRAS protein activator like-1 (RASAL1) exists in numerous human tissues and has been commonly demonstrated to act as a tumor suppressor in several cancers. This study aimed to identify the functional characteristics of RASAL1 in ovarian adenocarcinoma and a potential mechanism of action. We analyzed RASAL1 gene expression in ovarian adenocarcinoma samples and normal samples gained from the GEO and Oncomine databases respectively. Then the relationship between RASAL1 expression and overall survival (OS) was assessed using the Kaplan-Meier method. Furthermore, the biological effect of RASAL1 in ovarian adenocarcinoma cell lines was assessed by Quantitative real time-PCR (qRT-PCR), Cell Counting Kit-8 (CCK-8), western blot, wound healing and transwell assay. The statistical analysis showed patients with higher RASAL1 expression correlated with worse OS. The in vitro assays suggested knockdown of RASAL1 could inhibit cell proliferation, cell invasion and migration of ovarian adenocarcinoma. Moreover, the key proteins in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) signaling pathway were also decreased in ovarian adenocarcinoma cells with RASAL1 silencing. These findings provide promising evidence that RASAL1 may be not only a powerful biomarker but also an effective therapeutic target of ovarian adenocarcinoma.

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