MicroRNA-17-5p and MicroRNA-130b-3p Promote Radioresistance of Glioma Stem Cells by Targeting PTEN/AKT/HIF-1α Pathway-Controlled Phosphopentose Metabolism
Background. The radioresistance of glioma stem cells (GSCs) is related to some microRNAs (miRs) generated by radiation. This study aimed to investigate the effects of miR-17-5p and miR-130b-3p on the radiosensitivity of GSCs. Methods. miR-17-5p and miR-130b-3p expressions in SU3 and SU3-5R cells wer...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2023/6660072 |
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| author | Tao Xie Yu-Hao Ding Jun Dong Xi-An Fu |
| author_facet | Tao Xie Yu-Hao Ding Jun Dong Xi-An Fu |
| author_sort | Tao Xie |
| collection | DOAJ |
| description | Background. The radioresistance of glioma stem cells (GSCs) is related to some microRNAs (miRs) generated by radiation. This study aimed to investigate the effects of miR-17-5p and miR-130b-3p on the radiosensitivity of GSCs. Methods. miR-17-5p and miR-130b-3p expressions in SU3 and SU3-5R cells were determined. SU3 cells transfected with miR-17-5p or miR-130b-3p mimics or inhibitors were used to determine cell viability after irradiation as well as to examine changes of supernatant glucose, intracellular glucose 6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6-PGDH), reduced nicotinamide adenine dinucleotide phosphate (NADPH), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), phosphatase and tensin homolog (PTEN), hypoxia-inducible factor-1α (HIF-1α), glucose transporter (GLUT)-1/3, protein kinase B (AKT), and p-AKT levels. The target gene of the two miRs was verified by luciferase reporter gene assay. Results. miR-17-5p and miR-130b-3p expressions in the radiation-resistant SU3-5R cells or 8 Gy irradiation-treated SU3 cells were high. After transfection of SU3 cells with miR-17-5p or miR-130b-3p mimics, cell viability, intracellular HIF-1α, GLUT-1/3, AKT, and p-AKT protein expressions, and intracellular G6PDH, 6-PGDH, NADPH, GSH-Px, and GSH levels were high, whereas intracellular PTEN expression and supernatant glucose were low. The opposite effects were also observed in the two miR inhibitors-transfected SU3 cells. Further study confirmed that miR-17-5p or miR-130b-3p could directly bind with the PTEN. Conclusion. Radiation-induced miR-17-5p and miR-130b-3p might cause the radioresistance of GSCs, and the mechanisms were associated with the enhancement of antioxidant production, which was from the increments of AKT/HIF-1α signaling pathway-controlled glucose transmembrane transport and phosphopentose metabolism by targeting PTEN. |
| format | Article |
| id | doaj-art-fbe6ba6857c6434cb4f6c937df456d54 |
| institution | Kabale University |
| issn | 2210-7185 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-fbe6ba6857c6434cb4f6c937df456d542025-02-03T05:48:30ZengWileyAnalytical Cellular Pathology2210-71852023-01-01202310.1155/2023/6660072MicroRNA-17-5p and MicroRNA-130b-3p Promote Radioresistance of Glioma Stem Cells by Targeting PTEN/AKT/HIF-1α Pathway-Controlled Phosphopentose MetabolismTao Xie0Yu-Hao Ding1Jun Dong2Xi-An Fu3Department of NeurosurgeryDepartment of NeurosurgeryThe Experimental Center and Department of NeurosurgeryDepartment of NeurosurgeryBackground. The radioresistance of glioma stem cells (GSCs) is related to some microRNAs (miRs) generated by radiation. This study aimed to investigate the effects of miR-17-5p and miR-130b-3p on the radiosensitivity of GSCs. Methods. miR-17-5p and miR-130b-3p expressions in SU3 and SU3-5R cells were determined. SU3 cells transfected with miR-17-5p or miR-130b-3p mimics or inhibitors were used to determine cell viability after irradiation as well as to examine changes of supernatant glucose, intracellular glucose 6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6-PGDH), reduced nicotinamide adenine dinucleotide phosphate (NADPH), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), phosphatase and tensin homolog (PTEN), hypoxia-inducible factor-1α (HIF-1α), glucose transporter (GLUT)-1/3, protein kinase B (AKT), and p-AKT levels. The target gene of the two miRs was verified by luciferase reporter gene assay. Results. miR-17-5p and miR-130b-3p expressions in the radiation-resistant SU3-5R cells or 8 Gy irradiation-treated SU3 cells were high. After transfection of SU3 cells with miR-17-5p or miR-130b-3p mimics, cell viability, intracellular HIF-1α, GLUT-1/3, AKT, and p-AKT protein expressions, and intracellular G6PDH, 6-PGDH, NADPH, GSH-Px, and GSH levels were high, whereas intracellular PTEN expression and supernatant glucose were low. The opposite effects were also observed in the two miR inhibitors-transfected SU3 cells. Further study confirmed that miR-17-5p or miR-130b-3p could directly bind with the PTEN. Conclusion. Radiation-induced miR-17-5p and miR-130b-3p might cause the radioresistance of GSCs, and the mechanisms were associated with the enhancement of antioxidant production, which was from the increments of AKT/HIF-1α signaling pathway-controlled glucose transmembrane transport and phosphopentose metabolism by targeting PTEN.http://dx.doi.org/10.1155/2023/6660072 |
| spellingShingle | Tao Xie Yu-Hao Ding Jun Dong Xi-An Fu MicroRNA-17-5p and MicroRNA-130b-3p Promote Radioresistance of Glioma Stem Cells by Targeting PTEN/AKT/HIF-1α Pathway-Controlled Phosphopentose Metabolism Analytical Cellular Pathology |
| title | MicroRNA-17-5p and MicroRNA-130b-3p Promote Radioresistance of Glioma Stem Cells by Targeting PTEN/AKT/HIF-1α Pathway-Controlled Phosphopentose Metabolism |
| title_full | MicroRNA-17-5p and MicroRNA-130b-3p Promote Radioresistance of Glioma Stem Cells by Targeting PTEN/AKT/HIF-1α Pathway-Controlled Phosphopentose Metabolism |
| title_fullStr | MicroRNA-17-5p and MicroRNA-130b-3p Promote Radioresistance of Glioma Stem Cells by Targeting PTEN/AKT/HIF-1α Pathway-Controlled Phosphopentose Metabolism |
| title_full_unstemmed | MicroRNA-17-5p and MicroRNA-130b-3p Promote Radioresistance of Glioma Stem Cells by Targeting PTEN/AKT/HIF-1α Pathway-Controlled Phosphopentose Metabolism |
| title_short | MicroRNA-17-5p and MicroRNA-130b-3p Promote Radioresistance of Glioma Stem Cells by Targeting PTEN/AKT/HIF-1α Pathway-Controlled Phosphopentose Metabolism |
| title_sort | microrna 17 5p and microrna 130b 3p promote radioresistance of glioma stem cells by targeting pten akt hif 1α pathway controlled phosphopentose metabolism |
| url | http://dx.doi.org/10.1155/2023/6660072 |
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