Exosome-derived circ-001422 promotes tumor-associated macrophage M2 polarization to accelerate the progression of glioma

Abstract Cytokines, tumor cells, and tumor-associated macrophages play crucial roles in the composition of glioma tissue. Studies have demonstrated that certain cytokines can induce M2 polarization of tumor-associated macrophages and contribute to the progression of glioma. Nonetheless, the intricat...

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Main Authors: Wenpeng Cao, Zhirui Zeng, JianFei Sun, Yunhua Chen, FaGuang Kuang, Shipeng Luo, Jinzhi Lan, Shan Lei
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-024-07134-0
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author Wenpeng Cao
Zhirui Zeng
JianFei Sun
Yunhua Chen
FaGuang Kuang
Shipeng Luo
Jinzhi Lan
Shan Lei
author_facet Wenpeng Cao
Zhirui Zeng
JianFei Sun
Yunhua Chen
FaGuang Kuang
Shipeng Luo
Jinzhi Lan
Shan Lei
author_sort Wenpeng Cao
collection DOAJ
description Abstract Cytokines, tumor cells, and tumor-associated macrophages play crucial roles in the composition of glioma tissue. Studies have demonstrated that certain cytokines can induce M2 polarization of tumor-associated macrophages and contribute to the progression of glioma. Nonetheless, the intricate molecular interactions among cytokines, glioma cells, and tumor-associated macrophages remain largely unexplored. To investigate this cross-talk, a combination of RNA-sequencing, chromatin immunoprecipitation, immunoprecipitation, exosome isolation, and biological experiments were employed. Treatment with IL-6 significantly increased circ-001422 expression in glioma cells. A poorer prognosis was associated with elevated levels of circ-001422 in glioma tissues. Circ-001422 was transcribed directly by STAT3 through binding to its promoter. Circ-001422 exerted cancer-promoting functions when co-cultured with M2 macrophages. Furthermore, glioma cells were found to transfer circ-001422 to macrophages via an exosomal pathway, promoting M2 polarization. Mechanically, circ-001422 interacted with p300, resulting in STAT3 acetylation, thus promoting nuclear localization and transcriptional activity of STAT3/NF-κB and M2 macrophage polarization. In conclusion, glioma cells released exosomes enriched with circ-001422, which in turn induce M2 macrophage polarization by activating the STAT3/NF-κB pathway, thereby enhancing the aggressive characteristics of glioma cells. Targeting circ-001422 may represent a potential therapeutic approach for glioma.
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spelling doaj-art-36075fc15efc40d0b351355c33513f532024-11-17T12:42:41ZengNature PortfolioCommunications Biology2399-36422024-11-017111310.1038/s42003-024-07134-0Exosome-derived circ-001422 promotes tumor-associated macrophage M2 polarization to accelerate the progression of gliomaWenpeng Cao0Zhirui Zeng1JianFei Sun2Yunhua Chen3FaGuang Kuang4Shipeng Luo5Jinzhi Lan6Shan Lei7Key Laboratory of Human Brain bank for Functions and Diseases of Department of Education of Guizhou Province, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medicine, Guizhou Medical UniversityNational Demonstration Center for Experimental Basic Medical Education, School of Basic Medicine, Guizhou Medical UniversityKey Laboratory of Human Brain bank for Functions and Diseases of Department of Education of Guizhou Province, Guizhou Medical UniversityKey Laboratory of Human Brain bank for Functions and Diseases of Department of Education of Guizhou Province, Guizhou Medical UniversityKey Laboratory of Human Brain bank for Functions and Diseases of Department of Education of Guizhou Province, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medicine, Guizhou Medical UniversityDepartment of Physiology, School of Basic Medicine, Guizhou Medical UniversityAbstract Cytokines, tumor cells, and tumor-associated macrophages play crucial roles in the composition of glioma tissue. Studies have demonstrated that certain cytokines can induce M2 polarization of tumor-associated macrophages and contribute to the progression of glioma. Nonetheless, the intricate molecular interactions among cytokines, glioma cells, and tumor-associated macrophages remain largely unexplored. To investigate this cross-talk, a combination of RNA-sequencing, chromatin immunoprecipitation, immunoprecipitation, exosome isolation, and biological experiments were employed. Treatment with IL-6 significantly increased circ-001422 expression in glioma cells. A poorer prognosis was associated with elevated levels of circ-001422 in glioma tissues. Circ-001422 was transcribed directly by STAT3 through binding to its promoter. Circ-001422 exerted cancer-promoting functions when co-cultured with M2 macrophages. Furthermore, glioma cells were found to transfer circ-001422 to macrophages via an exosomal pathway, promoting M2 polarization. Mechanically, circ-001422 interacted with p300, resulting in STAT3 acetylation, thus promoting nuclear localization and transcriptional activity of STAT3/NF-κB and M2 macrophage polarization. In conclusion, glioma cells released exosomes enriched with circ-001422, which in turn induce M2 macrophage polarization by activating the STAT3/NF-κB pathway, thereby enhancing the aggressive characteristics of glioma cells. Targeting circ-001422 may represent a potential therapeutic approach for glioma.https://doi.org/10.1038/s42003-024-07134-0
spellingShingle Wenpeng Cao
Zhirui Zeng
JianFei Sun
Yunhua Chen
FaGuang Kuang
Shipeng Luo
Jinzhi Lan
Shan Lei
Exosome-derived circ-001422 promotes tumor-associated macrophage M2 polarization to accelerate the progression of glioma
Communications Biology
title Exosome-derived circ-001422 promotes tumor-associated macrophage M2 polarization to accelerate the progression of glioma
title_full Exosome-derived circ-001422 promotes tumor-associated macrophage M2 polarization to accelerate the progression of glioma
title_fullStr Exosome-derived circ-001422 promotes tumor-associated macrophage M2 polarization to accelerate the progression of glioma
title_full_unstemmed Exosome-derived circ-001422 promotes tumor-associated macrophage M2 polarization to accelerate the progression of glioma
title_short Exosome-derived circ-001422 promotes tumor-associated macrophage M2 polarization to accelerate the progression of glioma
title_sort exosome derived circ 001422 promotes tumor associated macrophage m2 polarization to accelerate the progression of glioma
url https://doi.org/10.1038/s42003-024-07134-0
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