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Exosomal miR‐6733‐5p mediates cross‐talk between glioblastoma stem cells and macrophages and promotes glioblastoma multiform progression synergistically

AIM: Exosomal miRNAs derived from glioblastoma stem cells (GSCs) are important mediators of immunosuppressive microenvironment formation in glioblastoma multiform (GBM), especially in M2‐like polarization of tumor‐associated macrophages (TAMs). However, the exact mechanisms by which GSCs‐derived exo...

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Autores principales: Huang, Shilu, Liu, Liang, Xu, Zhipeng, Liu, Xinglei, Wu, Anyi, Zhang, Xiaopei, Li, Zengyang, Li, Suwen, Li, Yongdong, Yuan, Jiaqi, Cheng, Shan, Li, Haoran, Dong, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651992/
https://www.ncbi.nlm.nih.gov/pubmed/37309294
http://dx.doi.org/10.1111/cns.14296
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author Huang, Shilu
Liu, Liang
Xu, Zhipeng
Liu, Xinglei
Wu, Anyi
Zhang, Xiaopei
Li, Zengyang
Li, Suwen
Li, Yongdong
Yuan, Jiaqi
Cheng, Shan
Li, Haoran
Dong, Jun
author_facet Huang, Shilu
Liu, Liang
Xu, Zhipeng
Liu, Xinglei
Wu, Anyi
Zhang, Xiaopei
Li, Zengyang
Li, Suwen
Li, Yongdong
Yuan, Jiaqi
Cheng, Shan
Li, Haoran
Dong, Jun
author_sort Huang, Shilu
collection PubMed
description AIM: Exosomal miRNAs derived from glioblastoma stem cells (GSCs) are important mediators of immunosuppressive microenvironment formation in glioblastoma multiform (GBM), especially in M2‐like polarization of tumor‐associated macrophages (TAMs). However, the exact mechanisms by which GSCs‐derived exosomes (GSCs‐exo) facilitate the remodeling of the immunosuppressive microenvironment of GBM have not been elucidated. METHODS: Transmission electron microscopy (TME) and nanoparticle tracking analysis (NTA) were applied to verify the existence of GSCs‐derived exosomes. Sphere formation assays, flow cytometry, and tumor xenograft transplantation assays were performed to identify the exact roles of exosomal miR‐6733‐5p. Then, the mechanisms of miR‐6733‐5p and its downstream target gene regulating crosstalk between GSCs cells and M2 macrophages were further investigated. RESULTS: GSCs‐derived exosomal miR‐6733‐5p induce macrophage M2 polarization of TAMs by positively targeting IGF2BP3 to activate the AKT signaling pathway, which further facilitates the self‐renewal and stemness of GSCs. CONCLUSION: GSCs secrete miR‐6733‐5p‐rich exosomes to induce M2‐like polarization of macrophages, as well as enhance GSCs stemness and promote malignant behaviors of GBM through IGF2BP3 activated AKT pathway. Targeting GSCs exosomal miR‐6733‐5p may provide a potential new strategy against GBM.
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spelling pubmed-106519922023-06-12 Exosomal miR‐6733‐5p mediates cross‐talk between glioblastoma stem cells and macrophages and promotes glioblastoma multiform progression synergistically Huang, Shilu Liu, Liang Xu, Zhipeng Liu, Xinglei Wu, Anyi Zhang, Xiaopei Li, Zengyang Li, Suwen Li, Yongdong Yuan, Jiaqi Cheng, Shan Li, Haoran Dong, Jun CNS Neurosci Ther Original Articles AIM: Exosomal miRNAs derived from glioblastoma stem cells (GSCs) are important mediators of immunosuppressive microenvironment formation in glioblastoma multiform (GBM), especially in M2‐like polarization of tumor‐associated macrophages (TAMs). However, the exact mechanisms by which GSCs‐derived exosomes (GSCs‐exo) facilitate the remodeling of the immunosuppressive microenvironment of GBM have not been elucidated. METHODS: Transmission electron microscopy (TME) and nanoparticle tracking analysis (NTA) were applied to verify the existence of GSCs‐derived exosomes. Sphere formation assays, flow cytometry, and tumor xenograft transplantation assays were performed to identify the exact roles of exosomal miR‐6733‐5p. Then, the mechanisms of miR‐6733‐5p and its downstream target gene regulating crosstalk between GSCs cells and M2 macrophages were further investigated. RESULTS: GSCs‐derived exosomal miR‐6733‐5p induce macrophage M2 polarization of TAMs by positively targeting IGF2BP3 to activate the AKT signaling pathway, which further facilitates the self‐renewal and stemness of GSCs. CONCLUSION: GSCs secrete miR‐6733‐5p‐rich exosomes to induce M2‐like polarization of macrophages, as well as enhance GSCs stemness and promote malignant behaviors of GBM through IGF2BP3 activated AKT pathway. Targeting GSCs exosomal miR‐6733‐5p may provide a potential new strategy against GBM. John Wiley and Sons Inc. 2023-06-12 /pmc/articles/PMC10651992/ /pubmed/37309294 http://dx.doi.org/10.1111/cns.14296 Text en © 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Huang, Shilu
Liu, Liang
Xu, Zhipeng
Liu, Xinglei
Wu, Anyi
Zhang, Xiaopei
Li, Zengyang
Li, Suwen
Li, Yongdong
Yuan, Jiaqi
Cheng, Shan
Li, Haoran
Dong, Jun
Exosomal miR‐6733‐5p mediates cross‐talk between glioblastoma stem cells and macrophages and promotes glioblastoma multiform progression synergistically
title Exosomal miR‐6733‐5p mediates cross‐talk between glioblastoma stem cells and macrophages and promotes glioblastoma multiform progression synergistically
title_full Exosomal miR‐6733‐5p mediates cross‐talk between glioblastoma stem cells and macrophages and promotes glioblastoma multiform progression synergistically
title_fullStr Exosomal miR‐6733‐5p mediates cross‐talk between glioblastoma stem cells and macrophages and promotes glioblastoma multiform progression synergistically
title_full_unstemmed Exosomal miR‐6733‐5p mediates cross‐talk between glioblastoma stem cells and macrophages and promotes glioblastoma multiform progression synergistically
title_short Exosomal miR‐6733‐5p mediates cross‐talk between glioblastoma stem cells and macrophages and promotes glioblastoma multiform progression synergistically
title_sort exosomal mir‐6733‐5p mediates cross‐talk between glioblastoma stem cells and macrophages and promotes glioblastoma multiform progression synergistically
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651992/
https://www.ncbi.nlm.nih.gov/pubmed/37309294
http://dx.doi.org/10.1111/cns.14296
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