The genotypic and phenotypic impact of hypoxia microenvironment on glioblastoma cell lines.
Brain Neoplasms
/ genetics
Cell Line, Tumor
Down-Regulation
Genotype
Glioblastoma
/ genetics
Glucose Transporter Type 1
/ metabolism
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ metabolism
MicroRNAs
/ metabolism
Octamer Transcription Factor-3
/ metabolism
Phenotype
Proto-Oncogene Proteins c-bcl-2
/ metabolism
SOXB1 Transcription Factors
/ metabolism
Survivin
/ metabolism
Tumor Hypoxia
/ genetics
Tumor Microenvironment
/ genetics
Up-Regulation
Vascular Endothelial Growth Factor A
/ metabolism
Glioblastoma
Stem-like state
Tumorigenesis
hypoxia microenvironment
miRNAs
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
19 Nov 2021
19 Nov 2021
Historique:
received:
04
03
2021
accepted:
04
11
2021
entrez:
20
11
2021
pubmed:
21
11
2021
medline:
22
2
2022
Statut:
epublish
Résumé
Glioblastoma is a fatal brain tumour with a poor patient survival outcome. Hypoxia has been shown to reprogram cells towards a stem cell phenotype associated with self-renewal and drug resistance properties. Activation of hypoxia-inducible factors (HIFs) helps in cellular adaptation mechanisms under hypoxia. Similarly, miRNAs are known to be dysregulated in GBM have been shown to act as critical mediators of the hypoxic response and to regulate key processes involved in tumorigenesis. Glioblastoma (GBM) cells were exposed to oxygen deprivation to mimic a tumour microenvironment and different cell aspects were analysed such as morphological changes and gene expression of miRNAs and survival genes known to be associated with tumorigenesis. It was observed that miR-128a-3p, miR-34-5p, miR-181a/b/c, were down-regulated in 6 GBM cell lines while miR-17-5p and miR-221-3p were upregulated when compared to a non-GBM control. When the same GBM cell lines were cultured under hypoxic microenvironment, a further 4-10-fold downregulation was observed for miR-34-5p, miR-128a-3p and 181a/b/c while a 3-6-fold upregulation was observed for miR-221-3p and 17-5p for most of the cells. Furthermore, there was an increased expression of SOX2 and Oct4, GLUT-1, VEGF, Bcl-2 and survivin, which are associated with a stem-like state, increased metabolism, altered angiogenesis and apoptotic escape, respectively. This study shows that by mimicking a tumour microenvironment, miRNAs are dysregulated, stemness factors are induced and alteration of the survival genes necessary for the cells to adapt to the micro-environmental factors occurs. Collectively, these results might contribute to GBM aggressiveness.
Sections du résumé
BACKGROUND
BACKGROUND
Glioblastoma is a fatal brain tumour with a poor patient survival outcome. Hypoxia has been shown to reprogram cells towards a stem cell phenotype associated with self-renewal and drug resistance properties. Activation of hypoxia-inducible factors (HIFs) helps in cellular adaptation mechanisms under hypoxia. Similarly, miRNAs are known to be dysregulated in GBM have been shown to act as critical mediators of the hypoxic response and to regulate key processes involved in tumorigenesis.
METHODS
METHODS
Glioblastoma (GBM) cells were exposed to oxygen deprivation to mimic a tumour microenvironment and different cell aspects were analysed such as morphological changes and gene expression of miRNAs and survival genes known to be associated with tumorigenesis.
RESULTS
RESULTS
It was observed that miR-128a-3p, miR-34-5p, miR-181a/b/c, were down-regulated in 6 GBM cell lines while miR-17-5p and miR-221-3p were upregulated when compared to a non-GBM control. When the same GBM cell lines were cultured under hypoxic microenvironment, a further 4-10-fold downregulation was observed for miR-34-5p, miR-128a-3p and 181a/b/c while a 3-6-fold upregulation was observed for miR-221-3p and 17-5p for most of the cells. Furthermore, there was an increased expression of SOX2 and Oct4, GLUT-1, VEGF, Bcl-2 and survivin, which are associated with a stem-like state, increased metabolism, altered angiogenesis and apoptotic escape, respectively.
CONCLUSION
CONCLUSIONS
This study shows that by mimicking a tumour microenvironment, miRNAs are dysregulated, stemness factors are induced and alteration of the survival genes necessary for the cells to adapt to the micro-environmental factors occurs. Collectively, these results might contribute to GBM aggressiveness.
Identifiants
pubmed: 34798868
doi: 10.1186/s12885-021-08978-z
pii: 10.1186/s12885-021-08978-z
pmc: PMC8605580
doi:
Substances chimiques
Glucose Transporter Type 1
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
MIRN128 microRNA, human
0
MIRN17 microRNA, human
0
MIRN221 microRNA, human
0
MIRN34 microRNA, human
0
MIrn181 microRNA, human
0
MicroRNAs
0
Octamer Transcription Factor-3
0
POU5F1 protein, human
0
Proto-Oncogene Proteins c-bcl-2
0
SOX2 protein, human
0
SOXB1 Transcription Factors
0
Survivin
0
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1248Informations de copyright
© 2021. The Author(s).
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