microRNA-27a-3p delivered by extracellular vesicles from glioblastoma cells induces M2 macrophage polarization via the EZH1/KDM3A/CTGF axis
Abstract Glioblastoma (GBM) cell-derived extracellular vesicles (EVs) have been demonstrated to modulate tumor microenvironment. In the present study, we attempted to discuss the role of hsa-microRNA-27a-3p (miR-27a-3p) delivered by GBM-EVs in M2 macrophage polarization. The isolated GBM-EVs were co...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-05-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-01035-z |
| _version_ | 1811235484708372480 |
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| author | Guifang Zhao Hongquan Yu Lijuan Ding Weiyao Wang Huan Wang Yao Hu Lingsha Qin Guangce Deng Buqing Xie Guofeng Li Ling Qi |
| author_facet | Guifang Zhao Hongquan Yu Lijuan Ding Weiyao Wang Huan Wang Yao Hu Lingsha Qin Guangce Deng Buqing Xie Guofeng Li Ling Qi |
| author_sort | Guifang Zhao |
| collection | DOAJ |
| description | Abstract Glioblastoma (GBM) cell-derived extracellular vesicles (EVs) have been demonstrated to modulate tumor microenvironment. In the present study, we attempted to discuss the role of hsa-microRNA-27a-3p (miR-27a-3p) delivered by GBM-EVs in M2 macrophage polarization. The isolated GBM-EVs were co-cultured with macrophages. After co-culture under normoxia/hypoxia, the effect of EV-derived hsa-miR-27a-3p on GBM cell biological processes was analyzed. Additionally, the target genes of hsa-miR-27a-3p were predicted. Moreover, the binding of enhancer of zeste homologue 1 (EZH1) to lysine-specific demethylase 3A (KDM3A) promoter region and the interaction between KDM3A and connective tissue growth factor (CTGF) were analyzed. GBM mouse models were established to verify the functions of EV-derived hsa-miR-27a-3p in vivo. We found increased hsa-miR-27a-3p in GBM tissues as well as GBM-EVs, which induced M2 polarization, thus promoting proliferative, migrative and invasive potentials of GBM cells. hsa-miR-27a-3p targeted EZH1 and promoted KDM3A expression to elevate the CTGF expression. GBM-EV-delivered hsa-miR-27a-3p promoted the KDM3A-upregulated CTGF by downregulating EZH1, thereby promoting M2 macrophage polarization and development of GBM in vivo. We demonstrated that EV-derived hsa-miR-27a-3p may promote M2 macrophage polarization to induce GBM. |
| first_indexed | 2024-04-12T11:52:38Z |
| format | Article |
| id | doaj.art-76ac5909a2494292b15754c58142fe9b |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-12T11:52:38Z |
| publishDate | 2022-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-76ac5909a2494292b15754c58142fe9b2022-12-22T03:34:08ZengNature Publishing GroupCell Death Discovery2058-77162022-05-018111210.1038/s41420-022-01035-zmicroRNA-27a-3p delivered by extracellular vesicles from glioblastoma cells induces M2 macrophage polarization via the EZH1/KDM3A/CTGF axisGuifang Zhao0Hongquan Yu1Lijuan Ding2Weiyao Wang3Huan Wang4Yao Hu5Lingsha Qin6Guangce Deng7Buqing Xie8Guofeng Li9Ling Qi10The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalDepartment of Oncological Neurosurgery, the First Hospital of Jilin UniversityDepartment of Oncological Neurosurgery, the First Hospital of Jilin UniversityJilin Medical UniversityThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalThe Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s HospitalAbstract Glioblastoma (GBM) cell-derived extracellular vesicles (EVs) have been demonstrated to modulate tumor microenvironment. In the present study, we attempted to discuss the role of hsa-microRNA-27a-3p (miR-27a-3p) delivered by GBM-EVs in M2 macrophage polarization. The isolated GBM-EVs were co-cultured with macrophages. After co-culture under normoxia/hypoxia, the effect of EV-derived hsa-miR-27a-3p on GBM cell biological processes was analyzed. Additionally, the target genes of hsa-miR-27a-3p were predicted. Moreover, the binding of enhancer of zeste homologue 1 (EZH1) to lysine-specific demethylase 3A (KDM3A) promoter region and the interaction between KDM3A and connective tissue growth factor (CTGF) were analyzed. GBM mouse models were established to verify the functions of EV-derived hsa-miR-27a-3p in vivo. We found increased hsa-miR-27a-3p in GBM tissues as well as GBM-EVs, which induced M2 polarization, thus promoting proliferative, migrative and invasive potentials of GBM cells. hsa-miR-27a-3p targeted EZH1 and promoted KDM3A expression to elevate the CTGF expression. GBM-EV-delivered hsa-miR-27a-3p promoted the KDM3A-upregulated CTGF by downregulating EZH1, thereby promoting M2 macrophage polarization and development of GBM in vivo. We demonstrated that EV-derived hsa-miR-27a-3p may promote M2 macrophage polarization to induce GBM.https://doi.org/10.1038/s41420-022-01035-z |
| spellingShingle | Guifang Zhao Hongquan Yu Lijuan Ding Weiyao Wang Huan Wang Yao Hu Lingsha Qin Guangce Deng Buqing Xie Guofeng Li Ling Qi microRNA-27a-3p delivered by extracellular vesicles from glioblastoma cells induces M2 macrophage polarization via the EZH1/KDM3A/CTGF axis Cell Death Discovery |
| title | microRNA-27a-3p delivered by extracellular vesicles from glioblastoma cells induces M2 macrophage polarization via the EZH1/KDM3A/CTGF axis |
| title_full | microRNA-27a-3p delivered by extracellular vesicles from glioblastoma cells induces M2 macrophage polarization via the EZH1/KDM3A/CTGF axis |
| title_fullStr | microRNA-27a-3p delivered by extracellular vesicles from glioblastoma cells induces M2 macrophage polarization via the EZH1/KDM3A/CTGF axis |
| title_full_unstemmed | microRNA-27a-3p delivered by extracellular vesicles from glioblastoma cells induces M2 macrophage polarization via the EZH1/KDM3A/CTGF axis |
| title_short | microRNA-27a-3p delivered by extracellular vesicles from glioblastoma cells induces M2 macrophage polarization via the EZH1/KDM3A/CTGF axis |
| title_sort | microrna 27a 3p delivered by extracellular vesicles from glioblastoma cells induces m2 macrophage polarization via the ezh1 kdm3a ctgf axis |
| url | https://doi.org/10.1038/s41420-022-01035-z |
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