Tumor‐derived exosomal miR‐19b‐3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway

Abstract Numerous reports have elucidated the important participation of exosomes in the communication between tumor cells and other cancer‐related cells including tumor‐associated macrophages (TAMs) in microenvironment. However, the interchange of exosomes between tumor cells and TAMs in the progre...

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Autores principales:	Jing Chen, Kai Zhang, Yingru Zhi, Yin Wu, Baoan Chen, Jinyu Bai, Xuerong Wang
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	exosome hippo signaling pathway lung adenocarcinoma M2 macrophage polarization miR‐19b‐3p Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/41c2f090997b436b90c9c741e933115b
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spelling	oai:doaj.org-article:41c2f090997b436b90c9c741e933115b2021-11-11T12:06:39ZTumor‐derived exosomal miR‐19b‐3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway2001-132610.1002/ctm2.478https://doaj.org/article/41c2f090997b436b90c9c741e933115b2021-09-01T00:00:00Zhttps://doi.org/10.1002/ctm2.478https://doaj.org/toc/2001-1326Abstract Numerous reports have elucidated the important participation of exosomes in the communication between tumor cells and other cancer‐related cells including tumor‐associated macrophages (TAMs) in microenvironment. However, the interchange of exosomes between tumor cells and TAMs in the progression of lung adenocarcinoma (LUAD) remains largely enigmatic. Herein, we discovered that LUAD cells induced the M2 polarization of TAMs and the M2‐polarized macrophages facilitated LUAD cell invasion and migration and tumor metastasis in vivo. In detail, LUAD cells secreted exosomes to transport miR‐19b‐3p into TAMs so that miR‐19b‐3p targeted PTPRD and inhibited the PTPRD‐mediated dephosphorylation of STAT3 in TAMs, leading to STAT3 activation and M2 polarization. Also, the activated STAT3 transcriptionally induced LINC00273 in M2 macrophages and exosomal LINC00273 was transferred into LUAD cells. In LUAD cells, LINC00273 recruited NEDD4 to facilitate LATS2 ubiquitination and degradation, so that the Hippo pathway was inactivated and YAP induced the transcription of RBMX. RBMX bound to miR‐19b‐3p to facilitate the packaging of miR‐19b‐3p into LUAD cell‐derived exosomes. Collectively, our results revealed the mechanism underlying the interactive communication between LUAD cells and TAMs through elucidating the exchange of exosomal miR‐19b‐3p and LINC00273 and proved the prometastatic effect of the interchange between two cells. These discoveries opened a new vision for developing LUAD treatment.Jing ChenKai ZhangYingru ZhiYin WuBaoan ChenJinyu BaiXuerong WangWileyarticleexosomehippo signaling pathwaylung adenocarcinomaM2 macrophage polarizationmiR‐19b‐3pMedicine (General)R5-920ENClinical and Translational Medicine, Vol 11, Iss 9, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	exosome hippo signaling pathway lung adenocarcinoma M2 macrophage polarization miR‐19b‐3p Medicine (General) R5-920
spellingShingle	exosome hippo signaling pathway lung adenocarcinoma M2 macrophage polarization miR‐19b‐3p Medicine (General) R5-920 Jing Chen Kai Zhang Yingru Zhi Yin Wu Baoan Chen Jinyu Bai Xuerong Wang Tumor‐derived exosomal miR‐19b‐3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway
description	Abstract Numerous reports have elucidated the important participation of exosomes in the communication between tumor cells and other cancer‐related cells including tumor‐associated macrophages (TAMs) in microenvironment. However, the interchange of exosomes between tumor cells and TAMs in the progression of lung adenocarcinoma (LUAD) remains largely enigmatic. Herein, we discovered that LUAD cells induced the M2 polarization of TAMs and the M2‐polarized macrophages facilitated LUAD cell invasion and migration and tumor metastasis in vivo. In detail, LUAD cells secreted exosomes to transport miR‐19b‐3p into TAMs so that miR‐19b‐3p targeted PTPRD and inhibited the PTPRD‐mediated dephosphorylation of STAT3 in TAMs, leading to STAT3 activation and M2 polarization. Also, the activated STAT3 transcriptionally induced LINC00273 in M2 macrophages and exosomal LINC00273 was transferred into LUAD cells. In LUAD cells, LINC00273 recruited NEDD4 to facilitate LATS2 ubiquitination and degradation, so that the Hippo pathway was inactivated and YAP induced the transcription of RBMX. RBMX bound to miR‐19b‐3p to facilitate the packaging of miR‐19b‐3p into LUAD cell‐derived exosomes. Collectively, our results revealed the mechanism underlying the interactive communication between LUAD cells and TAMs through elucidating the exchange of exosomal miR‐19b‐3p and LINC00273 and proved the prometastatic effect of the interchange between two cells. These discoveries opened a new vision for developing LUAD treatment.
format	article
author	Jing Chen Kai Zhang Yingru Zhi Yin Wu Baoan Chen Jinyu Bai Xuerong Wang
author_facet	Jing Chen Kai Zhang Yingru Zhi Yin Wu Baoan Chen Jinyu Bai Xuerong Wang
author_sort	Jing Chen
title	Tumor‐derived exosomal miR‐19b‐3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway
title_short	Tumor‐derived exosomal miR‐19b‐3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway
title_full	Tumor‐derived exosomal miR‐19b‐3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway
title_fullStr	Tumor‐derived exosomal miR‐19b‐3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway
title_full_unstemmed	Tumor‐derived exosomal miR‐19b‐3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway
title_sort	tumor‐derived exosomal mir‐19b‐3p facilitates m2 macrophage polarization and exosomal linc00273 secretion to promote lung adenocarcinoma metastasis via hippo pathway
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/41c2f090997b436b90c9c741e933115b
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Tumor‐derived exosomal miR‐19b‐3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway

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