The genotypic and phenotypic impact of hypoxia microenvironment on glioblastoma cell lines
Abstract 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 adaptat...
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2021
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oai:doaj.org-article:20243c366e754f0681fc81ee1a1413ea2021-11-21T12:30:17ZThe genotypic and phenotypic impact of hypoxia microenvironment on glioblastoma cell lines10.1186/s12885-021-08978-z1471-2407https://doaj.org/article/20243c366e754f0681fc81ee1a1413ea2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08978-zhttps://doaj.org/toc/1471-2407Abstract 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 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 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 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.Lucy Wanjiku MachariaWanjiru MuriithiCarlos Pilotto HemingDennis Kirii NyagaVeronica AranMarianne Wanjiru MureithiValeria Pereira FerrerAttilio PanePaulo Niemeyer FilhoVivaldo Moura-NetoBMCarticleGlioblastomaTumorigenesishypoxia microenvironmentmiRNAsStem-like stateNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-20 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Glioblastoma Tumorigenesis hypoxia microenvironment miRNAs Stem-like state Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
Glioblastoma Tumorigenesis hypoxia microenvironment miRNAs Stem-like state Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Lucy Wanjiku Macharia Wanjiru Muriithi Carlos Pilotto Heming Dennis Kirii Nyaga Veronica Aran Marianne Wanjiru Mureithi Valeria Pereira Ferrer Attilio Pane Paulo Niemeyer Filho Vivaldo Moura-Neto The genotypic and phenotypic impact of hypoxia microenvironment on glioblastoma cell lines |
| description |
Abstract 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 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 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 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. |
| format |
article |
| author |
Lucy Wanjiku Macharia Wanjiru Muriithi Carlos Pilotto Heming Dennis Kirii Nyaga Veronica Aran Marianne Wanjiru Mureithi Valeria Pereira Ferrer Attilio Pane Paulo Niemeyer Filho Vivaldo Moura-Neto |
| author_facet |
Lucy Wanjiku Macharia Wanjiru Muriithi Carlos Pilotto Heming Dennis Kirii Nyaga Veronica Aran Marianne Wanjiru Mureithi Valeria Pereira Ferrer Attilio Pane Paulo Niemeyer Filho Vivaldo Moura-Neto |
| author_sort |
Lucy Wanjiku Macharia |
| title |
The genotypic and phenotypic impact of hypoxia microenvironment on glioblastoma cell lines |
| title_short |
The genotypic and phenotypic impact of hypoxia microenvironment on glioblastoma cell lines |
| title_full |
The genotypic and phenotypic impact of hypoxia microenvironment on glioblastoma cell lines |
| title_fullStr |
The genotypic and phenotypic impact of hypoxia microenvironment on glioblastoma cell lines |
| title_full_unstemmed |
The genotypic and phenotypic impact of hypoxia microenvironment on glioblastoma cell lines |
| title_sort |
genotypic and phenotypic impact of hypoxia microenvironment on glioblastoma cell lines |
| publisher |
BMC |
| publishDate |
2021 |
| url |
https://doaj.org/article/20243c366e754f0681fc81ee1a1413ea |
| work_keys_str_mv |
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