M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway
Abstract Background Glioma, the most common primary brain tumor, account Preparing figures for 30 to 40% of all intracranial tumors. Herein, we aimed to study the effects of M2 macrophage-derived exosomal microRNAs (miRNAs) on glioma cells. Methods First, we identified seven differentially expressed...
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| Format: | Article |
| Language: | English |
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BMC
2021-03-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-021-02766-w |
| _version_ | 1818556497025564672 |
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| author | Jie Yao Zefen Wang Yong Cheng Chao Ma Yahua Zhong Yilei Xiao Xu Gao Zhiqiang Li |
| author_facet | Jie Yao Zefen Wang Yong Cheng Chao Ma Yahua Zhong Yilei Xiao Xu Gao Zhiqiang Li |
| author_sort | Jie Yao |
| collection | DOAJ |
| description | Abstract Background Glioma, the most common primary brain tumor, account Preparing figures for 30 to 40% of all intracranial tumors. Herein, we aimed to study the effects of M2 macrophage-derived exosomal microRNAs (miRNAs) on glioma cells. Methods First, we identified seven differentially expressed miRNAs in infiltrating macrophages and detected the expression of these seven miRNAs in M2 macrophages. We then selected hsa-miR-15a-5p (miR-15a) and hsa-miR-92a-3p (miR-92a) for follow-up studies, and confirmed that miR-15a and miR-92a were under-expressed in M2 macrophage exosomes. Subsequently, we demonstrated that M2 macrophage-derived exosomes promoted migration and invasion of glioma cells, while exosomal miR-15a and miR-92a had the opposite effects on glioma cells. Next, we performed the target gene prediction in four databases and conducted target gene validation by qRT-PCR, western blot and dual luciferase reporter gene assays. Results The results revealed that miR-15a and miR-92a were bound to CCND1 and RAP1B, respectively. Western blot assays demonstrated that interference with the expression of CCND1 or RAP1B reduced the phosphorylation level of AKT and mTOR, indicating that both CCND1 and RAP1B can activate the PI3K/AKT/mTOR signaling pathway. Conclusion Collectively, these findings indicate that M2 macrophage-derived exosomal miR-15a and miR-92a inhibit cell migration and invasion of glioma cells through PI3K/AKT/mTOR signaling pathway. |
| first_indexed | 2024-12-13T23:48:05Z |
| format | Article |
| id | doaj.art-ee06099b537d485392665c4dc8a9f9b6 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-13T23:48:05Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-ee06099b537d485392665c4dc8a9f9b62022-12-21T23:26:52ZengBMCJournal of Translational Medicine1479-58762021-03-0119111410.1186/s12967-021-02766-wM2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathwayJie Yao0Zefen Wang1Yong Cheng2Chao Ma3Yahua Zhong4Yilei Xiao5Xu Gao6Zhiqiang Li7Human Genetic Resources Conservation Center of Hubei ProvinceDepartment of Physiology, Wuhan University School of Basic Medical SciencesDepartment of Neurology, Hankou Hospital, General Hospital of Central Theater Command of Chinese People’s Liberation ArmyDepartment of Neurosurgery, Zhongnan Hospital of Wuhan UniversityDepartment of Oncology, Zhongnan Hospital of Wuhan UniversityDepartment of Neurosurgery, Liaocheng People’s HospitalDepartment of Neurosurgery, General Hospital of Northern Theater Command of People’s Liberation ArmyDepartment of Neurosurgery, Zhongnan Hospital of Wuhan UniversityAbstract Background Glioma, the most common primary brain tumor, account Preparing figures for 30 to 40% of all intracranial tumors. Herein, we aimed to study the effects of M2 macrophage-derived exosomal microRNAs (miRNAs) on glioma cells. Methods First, we identified seven differentially expressed miRNAs in infiltrating macrophages and detected the expression of these seven miRNAs in M2 macrophages. We then selected hsa-miR-15a-5p (miR-15a) and hsa-miR-92a-3p (miR-92a) for follow-up studies, and confirmed that miR-15a and miR-92a were under-expressed in M2 macrophage exosomes. Subsequently, we demonstrated that M2 macrophage-derived exosomes promoted migration and invasion of glioma cells, while exosomal miR-15a and miR-92a had the opposite effects on glioma cells. Next, we performed the target gene prediction in four databases and conducted target gene validation by qRT-PCR, western blot and dual luciferase reporter gene assays. Results The results revealed that miR-15a and miR-92a were bound to CCND1 and RAP1B, respectively. Western blot assays demonstrated that interference with the expression of CCND1 or RAP1B reduced the phosphorylation level of AKT and mTOR, indicating that both CCND1 and RAP1B can activate the PI3K/AKT/mTOR signaling pathway. Conclusion Collectively, these findings indicate that M2 macrophage-derived exosomal miR-15a and miR-92a inhibit cell migration and invasion of glioma cells through PI3K/AKT/mTOR signaling pathway.https://doi.org/10.1186/s12967-021-02766-wM2 macrophageExosomehsa-miR-15a-5phsa-miR-92a-3pGliomaPI3K/AKT/mTOR |
| spellingShingle | Jie Yao Zefen Wang Yong Cheng Chao Ma Yahua Zhong Yilei Xiao Xu Gao Zhiqiang Li M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway Journal of Translational Medicine M2 macrophage Exosome hsa-miR-15a-5p hsa-miR-92a-3p Glioma PI3K/AKT/mTOR |
| title | M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway |
| title_full | M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway |
| title_fullStr | M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway |
| title_full_unstemmed | M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway |
| title_short | M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway |
| title_sort | m2 macrophage derived exosomal micrornas inhibit cell migration and invasion in gliomas through pi3k akt mtor signaling pathway |
| topic | M2 macrophage Exosome hsa-miR-15a-5p hsa-miR-92a-3p Glioma PI3K/AKT/mTOR |
| url | https://doi.org/10.1186/s12967-021-02766-w |
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