TRIM8-driven transcriptomic profile of neural stem cells identified glioma-related nodal genes and pathways.
Animals
Carrier Proteins
/ metabolism
Central Nervous System
/ metabolism
Glioma
/ genetics
HEK293 Cells
High-Throughput Nucleotide Sequencing
Humans
Mice
Nerve Tissue Proteins
/ metabolism
Neural Stem Cells
/ metabolism
STAT3 Transcription Factor
/ metabolism
Transcriptome
Ubiquitin-Protein Ligases
E3 ubiquitin ligase
STAT3
TRIM8
transcriptome
Journal
Biochimica et biophysica acta. General subjects
ISSN: 1872-8006
Titre abrégé: Biochim Biophys Acta Gen Subj
Pays: Netherlands
ID NLM: 101731726
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
06
06
2018
revised:
26
11
2018
accepted:
03
12
2018
pubmed:
12
12
2018
medline:
1
10
2019
entrez:
12
12
2018
Statut:
ppublish
Résumé
We recently reported TRIM8, encoding an E3 ubiquitin ligase, as a gene aberrantly expressed in glioblastoma whose expression suppresses cell growth and induces a significant reduction of clonogenic potential in glioblastoma cell lines. we provided novel insights on TRIM8 functions by profiling the transcriptome of TRIM8-expressing primary mouse embryonal neural stem cells by RNA-sequencing and bioinformatic analysis. Functional analysis including luciferase assay, western blot, PCR arrays, Real time quantitative PCR were performed to validate the transcriptomic data. Our study identified enriched pathways related to the neurotransmission and to the central nervous system (CNS) functions, including axonal guidance, GABA receptor, Ephrin B, synaptic long-term potentiation/depression, and glutamate receptor signalling pathways. Finally, we provided additional evidence about the existence of a functional interactive crosstalk between TRIM8 and STAT3. Our results substantiate the role of TRIM8 in the brain functions through the dysregulation of genes involved in different CNS-related pathways, including JAK-STAT. This study provides novel insights on the physiological TRIM8 function by profiling for the first time the primary Neural Stem Cell over-expressing TRIM8 by using RNA-Sequencing methodology.
Sections du résumé
BACKGROUND
We recently reported TRIM8, encoding an E3 ubiquitin ligase, as a gene aberrantly expressed in glioblastoma whose expression suppresses cell growth and induces a significant reduction of clonogenic potential in glioblastoma cell lines.
METHODS
we provided novel insights on TRIM8 functions by profiling the transcriptome of TRIM8-expressing primary mouse embryonal neural stem cells by RNA-sequencing and bioinformatic analysis. Functional analysis including luciferase assay, western blot, PCR arrays, Real time quantitative PCR were performed to validate the transcriptomic data.
RESULTS
Our study identified enriched pathways related to the neurotransmission and to the central nervous system (CNS) functions, including axonal guidance, GABA receptor, Ephrin B, synaptic long-term potentiation/depression, and glutamate receptor signalling pathways. Finally, we provided additional evidence about the existence of a functional interactive crosstalk between TRIM8 and STAT3.
CONCLUSIONS
Our results substantiate the role of TRIM8 in the brain functions through the dysregulation of genes involved in different CNS-related pathways, including JAK-STAT.
GENERAL SIGNIFICANCE
This study provides novel insights on the physiological TRIM8 function by profiling for the first time the primary Neural Stem Cell over-expressing TRIM8 by using RNA-Sequencing methodology.
Identifiants
pubmed: 30528352
pii: S0304-4165(18)30364-7
doi: 10.1016/j.bbagen.2018.12.001
pii:
doi:
Substances chimiques
Carrier Proteins
0
Nerve Tissue Proteins
0
STAT3 Transcription Factor
0
Stat3 protein, mouse
0
Trim8 protein, mouse
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
491-501Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.