Inhibition of hypoxic exosomal miR-423-3p decreases glioma progression by restricting autophagy in astrocytes
Abstract The tumor microenvironment (TME) of gliomas comprises glioma cells and surrounding cells, such as astrocytes, macrophages, T cells, and neurons. In the TME, glioma cells can activate normal human astrocytes (NHAs) through the secretion of exosomes and the activation of astrocytes can furthe...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-04-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07576-2 |
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| author | Ziyi Tang Zhiwei Xue Xuchen Liu Yan Zhang Jiangli Zhao Junzhi Liu Lin Zhang Qindong Guo Bowen Feng Jiwei Wang Di Zhang Xingang Li |
| author_facet | Ziyi Tang Zhiwei Xue Xuchen Liu Yan Zhang Jiangli Zhao Junzhi Liu Lin Zhang Qindong Guo Bowen Feng Jiwei Wang Di Zhang Xingang Li |
| author_sort | Ziyi Tang |
| collection | DOAJ |
| description | Abstract The tumor microenvironment (TME) of gliomas comprises glioma cells and surrounding cells, such as astrocytes, macrophages, T cells, and neurons. In the TME, glioma cells can activate normal human astrocytes (NHAs) through the secretion of exosomes and the activation of astrocytes can further improve the progression of glioma, leading to a poor prognosis for patients. However, the molecular mechanisms underlying NHAs activation by gliomas remain largely unknown. It this study, glioma-derived exosomes (GDEs) play an important role in the modulation of autophagy and activation of NHAs. Compared with normoxic GDEs, hypoxic glioma-derived exosomes (H-GDEs) further improved autophagy and activation of astrocytes, which strongly promoted the progression of glioma cells. In an miRNA array between two types of exosomes from gliomas, miR-423-3p was highly expressed in H-GDEs and played an important role in autophagy, resulting in the activation of NHAs. The mechanism by which hypoxic glioma cells react with NHAs to create an immunosuppressive microenvironment was identified and 15d-PGJ2 was established as an effective inhibitor of miR-423-3p to suppress NHAs activation. These findings provide new insights into the diagnosis and treatment of gliomas by targeting autophagy and miR-423-3p expression. |
| format | Article |
| id | doaj-art-52c88ad0900b46e294f65897623d4d57 |
| institution | DOAJ |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-52c88ad0900b46e294f65897623d4d572025-08-20T03:10:08ZengNature Publishing GroupCell Death and Disease2041-48892025-04-0116111510.1038/s41419-025-07576-2Inhibition of hypoxic exosomal miR-423-3p decreases glioma progression by restricting autophagy in astrocytesZiyi Tang0Zhiwei Xue1Xuchen Liu2Yan Zhang3Jiangli Zhao4Junzhi Liu5Lin Zhang6Qindong Guo7Bowen Feng8Jiwei Wang9Di Zhang10Xingang Li11Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityAbstract The tumor microenvironment (TME) of gliomas comprises glioma cells and surrounding cells, such as astrocytes, macrophages, T cells, and neurons. In the TME, glioma cells can activate normal human astrocytes (NHAs) through the secretion of exosomes and the activation of astrocytes can further improve the progression of glioma, leading to a poor prognosis for patients. However, the molecular mechanisms underlying NHAs activation by gliomas remain largely unknown. It this study, glioma-derived exosomes (GDEs) play an important role in the modulation of autophagy and activation of NHAs. Compared with normoxic GDEs, hypoxic glioma-derived exosomes (H-GDEs) further improved autophagy and activation of astrocytes, which strongly promoted the progression of glioma cells. In an miRNA array between two types of exosomes from gliomas, miR-423-3p was highly expressed in H-GDEs and played an important role in autophagy, resulting in the activation of NHAs. The mechanism by which hypoxic glioma cells react with NHAs to create an immunosuppressive microenvironment was identified and 15d-PGJ2 was established as an effective inhibitor of miR-423-3p to suppress NHAs activation. These findings provide new insights into the diagnosis and treatment of gliomas by targeting autophagy and miR-423-3p expression.https://doi.org/10.1038/s41419-025-07576-2 |
| spellingShingle | Ziyi Tang Zhiwei Xue Xuchen Liu Yan Zhang Jiangli Zhao Junzhi Liu Lin Zhang Qindong Guo Bowen Feng Jiwei Wang Di Zhang Xingang Li Inhibition of hypoxic exosomal miR-423-3p decreases glioma progression by restricting autophagy in astrocytes Cell Death and Disease |
| title | Inhibition of hypoxic exosomal miR-423-3p decreases glioma progression by restricting autophagy in astrocytes |
| title_full | Inhibition of hypoxic exosomal miR-423-3p decreases glioma progression by restricting autophagy in astrocytes |
| title_fullStr | Inhibition of hypoxic exosomal miR-423-3p decreases glioma progression by restricting autophagy in astrocytes |
| title_full_unstemmed | Inhibition of hypoxic exosomal miR-423-3p decreases glioma progression by restricting autophagy in astrocytes |
| title_short | Inhibition of hypoxic exosomal miR-423-3p decreases glioma progression by restricting autophagy in astrocytes |
| title_sort | inhibition of hypoxic exosomal mir 423 3p decreases glioma progression by restricting autophagy in astrocytes |
| url | https://doi.org/10.1038/s41419-025-07576-2 |
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