Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enterovirus 71 induces pyroptosis of human neuroblastoma SH-SY5Y cells through miR-146a/ CXCR4 axis.

ABSTRACT: Enterovirus 71 (EV71) is a predominant causative pathogen of hand-foot-and-mouth disease (HFMD) in children. Compared with other HFMD-associated viruses, EV71 tends to induce more severe neurological complications and even death. However, the detailed mechanism of EV71 causes nervous system disorder is still unclear. In this study, we found that EV71 induced the GSDMD/NLRP3-mediated pyroptosis of SH-SY5Y cells through up-regulated miR-146a. Through bioinformatic analysis, we identified C-X-C chemokine receptor type 4 (CXCR4) as the potential target of miR-146a. We noticed that the expression of CXCR4 was regulated by miR-146a during EV71 infection. Moreover, our results show that over-expression of CXCR4 attenuated EV71-induced pyroptosis of SY-SY5Y cells. These results reveal a previously unrecognized mechanism in which EV71 induces nervous system cells damage through regulating miR-146a/CXCR4 mediated pyroptosis.

SUBMITTER: Guo H

PROVIDER: S-EPMC10121780 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Enterovirus 71 induces pyroptosis of human neuroblastoma SH-SY5Y cells through miR-146a/ CXCR4 axis.

Guo Hengzhong H Zhu Yangyang Y Zou Yu Y Li Chaozhi C Wang Ya Y De Gejing G Lu Lili L

Heliyon 20230329 4

Enterovirus 71 (EV71) is a predominant causative pathogen of hand-foot-and-mouth disease (HFMD) in children. Compared with other HFMD-associated viruses, EV71 tends to induce more severe neurological complications and even death. However, the detailed mechanism of EV71 causes nervous system disorder is still unclear. In this study, we found that EV71 induced the GSDMD/NLRP3-mediated pyroptosis of SH-SY5Y cells through up-regulated miR-146a. Through bioinformatic analysis, we identified C-X-C che ...[more]

PMID: 37095967

Similar Datasets

mRNA profiling in enterovirus type 71-infected SH-SY5Y cells after transfection with miR-1246 inhibitor

2014-07-31 | GSE45817 | GEO

mRNA profiling in enterovirus type 71-infected SH-SY5Y cells after transfection with miR-1246 inhibitor

Project description:Today, the pathogenesis of human enterovirus type 71 (HEV71) infection in human central neural system remains unclear. HEV71 is the major pathogen of hand-foot-and-mouth disease (HFMD), and has been associated with severe neurological disease and even death in infants and young children. We employed the human whole genome microarray analyze the mRNA profiling in human neuroblastoma cells SH-SY5Y infected with HEV71 after transfection. Firstly, SH-SY5Y cells were transfected wtih miR-1246 inhibitor and negtive control respectively using HiPerFect Transfection Reagent according to the manufacturer’s instructions. Then the cells were infected with HEV71 after transfection. After 12 hours infection, the cells were harvested to microarray analysis. The results showed the altered expression of mRNAs including up-regulated genes and down-regulated genes. Overall, this finding will help to understand the functional genes in HEV71-infected human neuroblastoma cells and miR-1246-virus-host interaction. SH-SY5Y cells were transfected wtih miR-1246 inhibitor and negtive control respectively using HiPerFect Transfection Reagent according to the manufacturer’s instructions. Then the cells were infected with HEV71 after transfection. After infection, the cells were harvested to microarray analysis. Total RNA of cells infected with HEV71 was extracted using the TRIZOL Reagent according to the manufacturer's instructions. Gene-expression profiling was performed for each pooling RNA sample separately on the GeneChip_ Porcine Genome Array at CapitalBio Corporation (Beijing, China).

2014-07-31 | E-GEOD-45817 | biostudies-arrayexpress

Transcriptomic analysis of SH-SY5Y cells in response to enterovirus type 71 infection

2013-10-31 | GSE45589 | GEO

Transcriptome of human neuroblastoma SH-SY5Y cells in response to 2B protein of enterovirus-A71.

Project description:Infection with enterovirus-A71 (EV-A71) can cause hand-foot-mouth disease associated with fatal neurological complications. The host response to EV-A71 has not yet been fully elucidated, thus, hampering the development of a precise therapeutic approach. A nonstructural 2B protein of EV-A71 has been reported to involve with calcium dysregulation and apoptosis induction in human neuroblastoma SH-SY5Y cells. However, the molecular mechanism has not been delineated. To address this, comprehensive study of the gene expression from SH-SY5Y cells transfected with EV-A71 2B was carried out by RNA sequencing and transcriptomic analysis. It was found that the signature of the upregulated genes of SH-SY5Y cells expressing EV-A71 2B involved the Ca2+-related signaling pathways participating gene expression, inflammatory response, apoptosis, and long-term potentiation of the neuron. Protein-protein interaction network analysis revealed that the products encoded by CCL2, RELB, BIRC3, and TNFRSF9 were the most significant hub proteins in the network. It indicated that EV-A71 2B protein might play a role in immunopathogenesis of the central nervous system (CNS) which probably associated with the non-canonical NF-κB pathway. The data suggest that transcriptomic profiling can provide novel information source for studying the neuropathogenesis of EV-A71 infection leading to development of an effective therapeutic measure for CNS complications.

| S-EPMC8810792 | biostudies-literature

Transcriptomic analysis of SH-SY5Y cells in response to enterovirus type 71 infection

Project description:Today, the pathogenesis of human enterovirus type 71 (HEV71) infection in human central neural system remains unclear. HEV71 is the major pathogen of hand-foot-and-mouth disease (HFMD), and has been associated with severe neurological disease and even death in infants and young children. We employed the human whole genome microarray analyze the transcriptome profiling inhuman neuroblastoma cells SH-SY5Y infected with HEV71. The results showed that HEV71 infection lead to altered expression of 161 human mRNAs including 74 up-regulated genes and 87 down-regulated genes. Then we found that the possible roles of the differentially regulated mRNAs in selected pathways including cell cycle/proliferation, apoptosis, and cytokine/chemokine responses by Bioinformatic analysis. Furthermore, we validated the microarray results by real-time RT-PCR with high identity. Overall, our results provided fundamental information about host response to HEV71 infection in human neuroblastoma cells, and this finding will help to understand the pathogenesis of HEV71 infection and virus-host interaction. Total RNA of cells infected with HEV71 was extracted using the TRIZOL Reagent according to the manufacturer's instructions. Gene-expression profiling was performed for each pooling RNA sample separately on the GeneChip_ Porcine Genome Array (Affymetrix) at CapitalBio Corporation (Beijing, China) in which GeneChip microarray service was certificated by Affymetrix.

2013-10-31 | E-GEOD-45589 | biostudies-arrayexpress

Butyrylcholinesterase in SH-SY5Y human neuroblastoma cells.

Project description:Cultured SH-SY5Y human neuroblastoma cells are used in neurotoxicity assays. These cells express markers of the cholinergic and dopaminergic systems. Acetylcholinesterase (AChE) activity has been reported in these cells. Neurotoxic organophosphate compounds that inhibit AChE, also inhibit butyrylcholinesterase (BChE). We confirmed the presence of AChE in the cell lysate by activity assays, Western blot, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) of immunopurified AChE. A nondenaturing gel stained for AChE activity identified the catalytically active AChE in SH-SY5Y cells as the unstable monomer. We also identified immature BChE in the cell lysate. The concentration of active BChE protein was similar to that of active AChE protein. The rate of substrate hydrolysis by AChE was 10-fold higher than substrate hydrolysis by BChE. The higher rate was due to the 10-fold higher specific activity of AChE over BChE (5000 units/mg for AChE; 500 units/mg for BChE). Neither cholinesterase was secreted. Tryptic peptides of immunopurified AChE and BChE were identified by LC-MS/MS on an Orbitrap Lumos Fusion mass spectrometer. The unfolded protein chaperone, binding immunoglobulin protein BiP/GRP78, was identified in the mass spectral data from all cholinesterase samples, suggesting that BiP was co-extracted with cholinesterase. This suggests that the cytoplasmic cholinesterases are immature forms of AChE and BChE that bind to BiP. It was concluded that SH-SY5Y cells express active AChE and active BChE, but the proteins do not mature to glycosylated tetramers.

| S-EPMC9124689 | biostudies-literature

PHD-2/HIF-1α axis mediates doxorubicin-induced angiogenesis in SH-SY5Y neuroblastoma microenvironment: a potential survival mechanism.

Project description:The response of neuroblastoma (NB) cells to chemotherapeutics and their influence on NB microenvironment remain incompletely understood. Herein, we examined the underlying molecular mechanism via which Doxorubicin, a chemotherapeutic agent used for NB treatment, promotes proangiogenic response in the SH-SY5Y microenvironment. Doxorubicin treatment at 1 µg/ml reduced SH-SY5Y cell proliferation and primed the apoptosis pathway. Unexpectedly, SH-SY5Y cells treated with doxorubicin upregulated their expression of the pro-angiogenic factors, including vascular endothelial growth factor (VEGF), platelets-derived growth factor (PDGF), and matrix metalloprotease-2 (MMP-2) and secretion of nitric oxide. To assess the functional angiogenesis of SH-SY5Y cells pre-treated with doxorubicin, an indirect co-culture system with human umbilical vein endothelial cells (HUVEC) was established. These HUVECs acquired enhanced proliferation, migration capacity, and tube formation capability and exhibited increased nitric oxide (NO) production, in addition to upregulated α-smooth muscle actin expression, suggesting enhanced contractility. In-ovo studies of the neo-angiogenic response of SH-SY5Y pre-treated with doxorubicin further show their promoted neo-angiogenesis as indicated by the generated blood vessels and histological analysis of CD31 expression. Inhibition of PHD-2 could be a potential target for doxorubicin, as indicated by molecular docking, molecular dynamics (MD) simulation, and MM-GBSA calculations, leading to hypoxia-inducible factor-1 alpha (HIF-1α) stabilization. Bioinformatics analyses and enrichment analyses of RNA-seq data revealed activation of Pi3K pathway which is further validated in-vitro. These results provide evidence of the unexpected pro-angiogenic response of SH-SY5Y cells to doxorubicin treatment and suggest the potential use of multi-modal therapeutic regimens for a more comprehensive approach to NB treatment.

| S-EPMC11876694 | biostudies-literature

Identification of ULK1 as a novel biomarker involved in miR-4487 and miR-595 regulation in neuroblastoma SH-SY5Y cell autophagy.

Project description:Autophagy, referring to an evolutionarily conserved, multi-step lysosomal degradation process, has been well-known to be initiated by Unc-51 like kinase 1 (ULK1) with some links to Parkinson's disease (PD). MicroRNAs (miRNAs), small and non-coding endogenous RNAs 22 ~ 24 nucleotides (nt) in length, have been demonstrated to play an essential role for modulating autophagy. Recently, the relationships between miRNAs and autophagy have been widely reported in PD; however, how microRNAs regulate autophagy still remains in its infancy. Thus, in this study, we computationally constructed the ULK1-regulated autophagic kinase subnetwork in PD and further identified ULK1 able to negatively regulate p70(S6K) in starvation-induced autophagy of neuroblastoma SH-SY5Y cells. Combination of in silico prediction and microarray analyses, we identified that miR-4487 and miR-595 could target ULK1 and experimentally verified they could negatively or positively regulate ULK1-mediated autophagy. In conclusion, these results may uncover the novel ULK1-p70(S6K) autophagic pathway, as well as miR-4487 and miR-595 as new ULK1 target miRNAs. Thus, these findings would provide a clue to explore ULK1 and its target miRNAs as potential biomarkers in the future PD therapy.

| S-EPMC4505320 | biostudies-literature

Transcriptome of human neuroblastoma SH-SY5Y cells in response to 2B protein of enterovirus-A71

Project description:Non-structural 2B protein of enterovirus-A71 has reported involving in intracellular Ca2+ manipulation and altering cellular homeostasis such as inducing cell death in human SH-SY5Y cells. The aim of the study is to profile transcriptomic signature of human neuroblastoma SH-SY5Y cells altered by EV-A71 2B protein using RNA-sequencing analysis. We generated mRNA expression profiles of SH-SY5Y cells transfected with EV-A71 2B protein fused with mCherry and FLAG tag protein (2BmCherry) and mCherry as well as parental SH-SY5Y cells. We find that 7 genes including CCL2, RELB, IL32, PLAT, PTGES, PHLDA1, and TNFRSF9 are uniquely overexpressed in 2BmCherry comparing to mCherry. Moreover, there were 333 upregulated and 333 downregulated genes showed significant different expression level in 2BmCherry transcriptome in comparison with SHSY5Y transcriptome but not in mCherry vs SHSY5Y comparison. Functional analysis showed that EV-A71 2B upregulated genes involved Ca2+-related signaling pathways participating gene expression, immune response, apoptosis, and long-term potentiation (synaptic adaptation) of neuron in the transfected SH-SY5Y cells.

2021-12-23 | GSE191270 | GEO

Neuroblastoma SH-SY5Y Cell Differentiation to Mature Neuron by AM580 Treatment.

Project description:Neuroblastoma is a type of developmental childhood cancer that arises from the neural crest. It is the most common pediatric solid tumor in the world. AM580 is a powerful cyto-differentiating molecule on acute promyelocytic leukemia cells and induced pluripotent stem cells, but its effect on neuroblastoma is still unknown. In this study, the neuronal differentiation impact of AM580 was investigated using the human neuroblastoma cell line SH-SY5Y as a model. AM580 successfully stimulated the SH-SY5Y cells to develop into neuron-like cells. Functional enrichment analysis of RNAseq data revealed that differentially expressed genes (DEGs) were substantially enriched for GO keywords and KEGG pathways linked to neuron development. Some potassium ion channel genes associated with neuronal excitation, such as KCNT1, were shown to be upregulated. Through the MEA tests, we found the AM580-induced neurons possessed electrical spikes as mature neurons. AM580 also induced the neuronal marker β-tubulin III and mature neurons marker Neurofilament H. Our study proved that AM580 can promote the differentiation of neurons and has the potential to treat neuroblastoma, neurodevelopmental and neurodegenerative diseases.

| S-EPMC9718880 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data