Extracellular RNA transfer from non‐malignant human cholangiocytes can promote cholangiocarcinoma growth

Extracellular vesicles (EV) within the cellular secretome are emerging as modulators of pathological processes involved in tumor growth through their ability to transfer donor‐derived RNA into recipient cells. While the effects of tumor and stromal cell EVs within the tumor microenvironment have bee...

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Autores principales:	Yu Ota, Kenji Takahashi, Shin Otake, Yosui Tamaki, Mitsuyoshi Okada, Irene Yan, Kazunobu Aso, Satoshi Fujii, Tushar Patel, Masakazu Haneda
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	epithelial‐mesenchymal transition extracellular vesicles microRNA secretome tumor microenvironment Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/eb92731c50a34026861aa9869e2ff1cc
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spelling	oai:doaj.org-article:eb92731c50a34026861aa9869e2ff1cc2021-12-01T13:36:12ZExtracellular RNA transfer from non‐malignant human cholangiocytes can promote cholangiocarcinoma growth2211-546310.1002/2211-5463.13294https://doaj.org/article/eb92731c50a34026861aa9869e2ff1cc2021-12-01T00:00:00Zhttps://doi.org/10.1002/2211-5463.13294https://doaj.org/toc/2211-5463Extracellular vesicles (EV) within the cellular secretome are emerging as modulators of pathological processes involved in tumor growth through their ability to transfer donor‐derived RNA into recipient cells. While the effects of tumor and stromal cell EVs within the tumor microenvironment have been studied, less is known about the contributions of normal, nontransformed cells. We examined the impact of EVs within the cellular secretome from nonmalignant cells on transformed cell growth and behavior in cholangiocarcinoma cells. These effects were enhanced in the presence of the pro‐fibrogenic mediator TGF‐β. We identified miR‐195 as a TGF‐β responsive miRNA in normal cells that can be transferred via EV to tumor cells and regulate cell growth, invasion, and migration. The effects of miR‐195 involve modulation of the epithelial–mesenchymal transition through direct effects on the transcription factor Snail. These studies provide in vitro and in vivo evidence for the impact of normal cellular secretome on transformed cell growth, show the importance of EV RNA transfer, and identify mechanisms of EV‐mediated transfer of miRNA as a contributor to tumor development, which may provide new therapeutic opportunities for targeting human cholangiocarcinoma.Yu OtaKenji TakahashiShin OtakeYosui TamakiMitsuyoshi OkadaIrene YanKazunobu AsoSatoshi FujiiTushar PatelMasakazu HanedaWileyarticleepithelial‐mesenchymal transitionextracellular vesiclesmicroRNAsecretometumor microenvironmentBiology (General)QH301-705.5ENFEBS Open Bio, Vol 11, Iss 12, Pp 3276-3292 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	epithelial‐mesenchymal transition extracellular vesicles microRNA secretome tumor microenvironment Biology (General) QH301-705.5
spellingShingle	epithelial‐mesenchymal transition extracellular vesicles microRNA secretome tumor microenvironment Biology (General) QH301-705.5 Yu Ota Kenji Takahashi Shin Otake Yosui Tamaki Mitsuyoshi Okada Irene Yan Kazunobu Aso Satoshi Fujii Tushar Patel Masakazu Haneda Extracellular RNA transfer from non‐malignant human cholangiocytes can promote cholangiocarcinoma growth
description	Extracellular vesicles (EV) within the cellular secretome are emerging as modulators of pathological processes involved in tumor growth through their ability to transfer donor‐derived RNA into recipient cells. While the effects of tumor and stromal cell EVs within the tumor microenvironment have been studied, less is known about the contributions of normal, nontransformed cells. We examined the impact of EVs within the cellular secretome from nonmalignant cells on transformed cell growth and behavior in cholangiocarcinoma cells. These effects were enhanced in the presence of the pro‐fibrogenic mediator TGF‐β. We identified miR‐195 as a TGF‐β responsive miRNA in normal cells that can be transferred via EV to tumor cells and regulate cell growth, invasion, and migration. The effects of miR‐195 involve modulation of the epithelial–mesenchymal transition through direct effects on the transcription factor Snail. These studies provide in vitro and in vivo evidence for the impact of normal cellular secretome on transformed cell growth, show the importance of EV RNA transfer, and identify mechanisms of EV‐mediated transfer of miRNA as a contributor to tumor development, which may provide new therapeutic opportunities for targeting human cholangiocarcinoma.
format	article
author	Yu Ota Kenji Takahashi Shin Otake Yosui Tamaki Mitsuyoshi Okada Irene Yan Kazunobu Aso Satoshi Fujii Tushar Patel Masakazu Haneda
author_facet	Yu Ota Kenji Takahashi Shin Otake Yosui Tamaki Mitsuyoshi Okada Irene Yan Kazunobu Aso Satoshi Fujii Tushar Patel Masakazu Haneda
author_sort	Yu Ota
title	Extracellular RNA transfer from non‐malignant human cholangiocytes can promote cholangiocarcinoma growth
title_short	Extracellular RNA transfer from non‐malignant human cholangiocytes can promote cholangiocarcinoma growth
title_full	Extracellular RNA transfer from non‐malignant human cholangiocytes can promote cholangiocarcinoma growth
title_fullStr	Extracellular RNA transfer from non‐malignant human cholangiocytes can promote cholangiocarcinoma growth
title_full_unstemmed	Extracellular RNA transfer from non‐malignant human cholangiocytes can promote cholangiocarcinoma growth
title_sort	extracellular rna transfer from non‐malignant human cholangiocytes can promote cholangiocarcinoma growth
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/eb92731c50a34026861aa9869e2ff1cc
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_version_	1718405149239541760

Extracellular RNA transfer from non‐malignant human cholangiocytes can promote cholangiocarcinoma growth

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