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Hypoxic lung adenocarcinoma‐derived exosomal miR‐1290 induces M2 macrophage polarization by targeting SOCS3

BACKGROUND: Exosomes are critical mediators of tumor cell‐microenvironment cross talk. However, the mechanisms by which hypoxic Lung adenocarcinoma (LUAD)‐derived exosomes modulate macrophage polarization remain largely unknown. The aim of this study was to investigate the effects of hypoxic LUAD‐de...

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Autores principales: Gu, Jiahui, Yang, Shengrui, Wang, Xueying, Wu, Yining, Wei, Jia, Xu, Jian
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/PMC10278512/
https://www.ncbi.nlm.nih.gov/pubmed/37081748
http://dx.doi.org/10.1002/cam4.5954
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author Gu, Jiahui
Yang, Shengrui
Wang, Xueying
Wu, Yining
Wei, Jia
Xu, Jian
author_facet Gu, Jiahui
Yang, Shengrui
Wang, Xueying
Wu, Yining
Wei, Jia
Xu, Jian
author_sort Gu, Jiahui
collection PubMed
description BACKGROUND: Exosomes are critical mediators of tumor cell‐microenvironment cross talk. However, the mechanisms by which hypoxic Lung adenocarcinoma (LUAD)‐derived exosomes modulate macrophage polarization remain largely unknown. The aim of this study was to investigate the effects of hypoxic LUAD‐derived exosome on macrophage polarization and explore the underlying molecular mechanism. MATERIALS AND METHODS: LUAD‐derived exosomes were isolated, and then confirmed by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Internalization of exosomes in macrophages was detected by confocal microscope. Gain‐ and loss‐of‐function experiments, rescue experiments, and xenograft models were performed to uncover the underlying mechanisms of exosomal miR‐1290 induced macrophage polarization in vitro and in vivo. RESULTS: miR‐1290 was enriched in hypoxic LUAD cancer cell‐derived exosomes and could be transferred to macrophages. Overexpression of miR‐1290 in macrophages‐induced polarization of M2 phenotype. Luciferase assay verified SOCS3 was the target of miR‐1290. Hypoxic LUAD cell‐derived exosomal miR‐1290 activated the STAT3 signaling pathway by targeting SOCS3 to promote M2 macrophage polarization. CONCLUSION: Hypoxic LUAD cells generate miR‐1290‐rich exosomes that promote M2 polarization of macrophages. Targeting exosomal miR‐1290 may provide a potential immunotherapeutic strategy for LUAD.
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spelling pubmed-102785122023-06-20 Hypoxic lung adenocarcinoma‐derived exosomal miR‐1290 induces M2 macrophage polarization by targeting SOCS3 Gu, Jiahui Yang, Shengrui Wang, Xueying Wu, Yining Wei, Jia Xu, Jian Cancer Med RESEARCH ARTICLES BACKGROUND: Exosomes are critical mediators of tumor cell‐microenvironment cross talk. However, the mechanisms by which hypoxic Lung adenocarcinoma (LUAD)‐derived exosomes modulate macrophage polarization remain largely unknown. The aim of this study was to investigate the effects of hypoxic LUAD‐derived exosome on macrophage polarization and explore the underlying molecular mechanism. MATERIALS AND METHODS: LUAD‐derived exosomes were isolated, and then confirmed by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Internalization of exosomes in macrophages was detected by confocal microscope. Gain‐ and loss‐of‐function experiments, rescue experiments, and xenograft models were performed to uncover the underlying mechanisms of exosomal miR‐1290 induced macrophage polarization in vitro and in vivo. RESULTS: miR‐1290 was enriched in hypoxic LUAD cancer cell‐derived exosomes and could be transferred to macrophages. Overexpression of miR‐1290 in macrophages‐induced polarization of M2 phenotype. Luciferase assay verified SOCS3 was the target of miR‐1290. Hypoxic LUAD cell‐derived exosomal miR‐1290 activated the STAT3 signaling pathway by targeting SOCS3 to promote M2 macrophage polarization. CONCLUSION: Hypoxic LUAD cells generate miR‐1290‐rich exosomes that promote M2 polarization of macrophages. Targeting exosomal miR‐1290 may provide a potential immunotherapeutic strategy for LUAD. John Wiley and Sons Inc. 2023-04-20 /pmc/articles/PMC10278512/ /pubmed/37081748 http://dx.doi.org/10.1002/cam4.5954 Text en © 2023 The Authors. Cancer Medicine 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 RESEARCH ARTICLES
Gu, Jiahui
Yang, Shengrui
Wang, Xueying
Wu, Yining
Wei, Jia
Xu, Jian
Hypoxic lung adenocarcinoma‐derived exosomal miR‐1290 induces M2 macrophage polarization by targeting SOCS3
title Hypoxic lung adenocarcinoma‐derived exosomal miR‐1290 induces M2 macrophage polarization by targeting SOCS3
title_full Hypoxic lung adenocarcinoma‐derived exosomal miR‐1290 induces M2 macrophage polarization by targeting SOCS3
title_fullStr Hypoxic lung adenocarcinoma‐derived exosomal miR‐1290 induces M2 macrophage polarization by targeting SOCS3
title_full_unstemmed Hypoxic lung adenocarcinoma‐derived exosomal miR‐1290 induces M2 macrophage polarization by targeting SOCS3
title_short Hypoxic lung adenocarcinoma‐derived exosomal miR‐1290 induces M2 macrophage polarization by targeting SOCS3
title_sort hypoxic lung adenocarcinoma‐derived exosomal mir‐1290 induces m2 macrophage polarization by targeting socs3
topic RESEARCH ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278512/
https://www.ncbi.nlm.nih.gov/pubmed/37081748
http://dx.doi.org/10.1002/cam4.5954
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