The miR-27a-3p/FTO axis modifies hypoxia-induced malignant behaviors of glioma cells
Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system (CNS) tumors. N6-methyladenine (m6A) RNA modification is a main type of RNA modification in eukaryotic cells. In this study, we find that the m6A RNA methylation eraser FTO is dramatically downregulated in gli...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2023-01-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2023002 |
| _version_ | 1797635798079635456 |
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| author | Du Peng Meng Li Liao Xinbin Liu Yi Mo Xin Gong Mengqi Liao Yiwei |
| author_facet | Du Peng Meng Li Liao Xinbin Liu Yi Mo Xin Gong Mengqi Liao Yiwei |
| author_sort | Du Peng |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system (CNS) tumors. N6-methyladenine (m6A) RNA modification is a main type of RNA modification in eukaryotic cells. In this study, we find that the m6A RNA methylation eraser FTO is dramatically downregulated in glioma samples and cell lines, particularly in intermediate and core regions and hypoxia-challenged glioma cells. In vitro, FTO overexpression inhibits the hypoxia-induced capacities of glioma cells to proliferate, migrate and invade, and decreases the percentage of cells with m6A RNA methylation. In vivo, FTO overexpression inhibits tumor growth in the xenograft model and decreases the protein levels of migration markers, including Vimentin and Twist. miR-27a-3p is upregulated within glioma intermediate and core regions and hypoxia-challenged glioma cells. miR-27a-3p inhibits the expression of FTO via direct binding to FTO. miR-27a-3p overexpression promotes hypoxia-challenged glioma cell aggressiveness, whereas FTO overexpression partially diminishes the oncogenic effects of miR-27a-3p overexpression. FTO overexpression promotes the nuclear translocation of FOXO3a and upregulates the expression levels of the FOXO3a downstream targets BIM, BNIP3, BCL-6, and PUMA, possibly by interacting with FOXO3a. Conclusively, FTO serves as a tumor suppressor in glioma by suppressing hypoxia-induced malignant behaviors of glioma cells, possibly by promoting the nuclear translocation of FOXO3a and upregulating FOXO3a downstream targets. miR-27a-3p is a major contributor to FTO downregulation in glioma under hypoxia. |
| first_indexed | 2024-03-11T12:25:28Z |
| format | Article |
| id | doaj.art-2b555f3932fa43eebff494ce9ceb1a37 |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:25:28Z |
| publishDate | 2023-01-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-2b555f3932fa43eebff494ce9ceb1a372023-11-06T08:59:53ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452023-01-015510311610.3724/abbs.202300220d259ccThe miR-27a-3p/FTO axis modifies hypoxia-induced malignant behaviors of glioma cellsDu Peng0Meng Li1Liao Xinbin2Liu Yi3Mo Xin4Gong Mengqi5Liao Yiwei6["National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China","Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China","Department of Neurosurgery, The Second Affiliated Hospital, Xinjiang Medical University, Urumqi 830063, China"]["Department of Radiology, Xiangya Hospital, Central South University, Changsha 410008, China"]["Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China"]["Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China"]["Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China"]["Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China"]["National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China","Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China"]Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system (CNS) tumors. N6-methyladenine (m6A) RNA modification is a main type of RNA modification in eukaryotic cells. In this study, we find that the m6A RNA methylation eraser FTO is dramatically downregulated in glioma samples and cell lines, particularly in intermediate and core regions and hypoxia-challenged glioma cells. In vitro, FTO overexpression inhibits the hypoxia-induced capacities of glioma cells to proliferate, migrate and invade, and decreases the percentage of cells with m6A RNA methylation. In vivo, FTO overexpression inhibits tumor growth in the xenograft model and decreases the protein levels of migration markers, including Vimentin and Twist. miR-27a-3p is upregulated within glioma intermediate and core regions and hypoxia-challenged glioma cells. miR-27a-3p inhibits the expression of FTO via direct binding to FTO. miR-27a-3p overexpression promotes hypoxia-challenged glioma cell aggressiveness, whereas FTO overexpression partially diminishes the oncogenic effects of miR-27a-3p overexpression. FTO overexpression promotes the nuclear translocation of FOXO3a and upregulates the expression levels of the FOXO3a downstream targets BIM, BNIP3, BCL-6, and PUMA, possibly by interacting with FOXO3a. Conclusively, FTO serves as a tumor suppressor in glioma by suppressing hypoxia-induced malignant behaviors of glioma cells, possibly by promoting the nuclear translocation of FOXO3a and upregulating FOXO3a downstream targets. miR-27a-3p is a major contributor to FTO downregulation in glioma under hypoxia. https://www.sciengine.com/doi/10.3724/abbs.2023002glioblastomam6A RNA methylationFTOmiR-27a-3phypoxia |
| spellingShingle | Du Peng Meng Li Liao Xinbin Liu Yi Mo Xin Gong Mengqi Liao Yiwei The miR-27a-3p/FTO axis modifies hypoxia-induced malignant behaviors of glioma cells Acta Biochimica et Biophysica Sinica glioblastoma m6A RNA methylation FTO miR-27a-3p hypoxia |
| title | The miR-27a-3p/FTO axis modifies hypoxia-induced malignant behaviors of glioma cells |
| title_full | The miR-27a-3p/FTO axis modifies hypoxia-induced malignant behaviors of glioma cells |
| title_fullStr | The miR-27a-3p/FTO axis modifies hypoxia-induced malignant behaviors of glioma cells |
| title_full_unstemmed | The miR-27a-3p/FTO axis modifies hypoxia-induced malignant behaviors of glioma cells |
| title_short | The miR-27a-3p/FTO axis modifies hypoxia-induced malignant behaviors of glioma cells |
| title_sort | mir 27a 3p fto axis modifies hypoxia induced malignant behaviors of glioma cells |
| topic | glioblastoma m6A RNA methylation FTO miR-27a-3p hypoxia |
| url | https://www.sciengine.com/doi/10.3724/abbs.2023002 |
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