p38 activation induces production of miR-146a and miR-31 to repress E-selectin expression and inhibit transendothelial migration of colon cancer cells

Abstract Extravasation of circulating cancer cells determines their metastatic potential. This process is initiated by the adhesion of cancer cells to vascular endothelial cells through specific interactions between endothelial adhesion receptors such as E-selectin and their ligands on cancer cells....

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Autores principales:	Liang Zhong, Jacques Huot, Martin J. Simard
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f2e4ef41a8f84b8cad6220c1adb09894
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spelling	oai:doaj.org-article:f2e4ef41a8f84b8cad6220c1adb098942021-12-02T11:41:03Zp38 activation induces production of miR-146a and miR-31 to repress E-selectin expression and inhibit transendothelial migration of colon cancer cells10.1038/s41598-018-20837-92045-2322https://doaj.org/article/f2e4ef41a8f84b8cad6220c1adb098942018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20837-9https://doaj.org/toc/2045-2322Abstract Extravasation of circulating cancer cells determines their metastatic potential. This process is initiated by the adhesion of cancer cells to vascular endothelial cells through specific interactions between endothelial adhesion receptors such as E-selectin and their ligands on cancer cells. In the present study, we show that miR-146a and miR-181b impede the expression of E-selectin by repressing the activity of its transcription factor NF-κB, thereby impairing the metastatic potentials of colon cancer cells by decreasing their adhesion to, and migration through, the endothelium. Among the two microRNAs, only miR-146a is activated by IL-1β, through the activation of p38, ERK and JNK MAP kinases, as well as their downstream transcription factors GATA2, c-Fos and c-Jun. Inhibiting p38 MAP kinase increases NF-κB activity, at least partially via miR-146a. Inhibiting p38 also increases the expression of E-selectin at the post-transcriptional level via decreasing miR-31, which targets E-selectin mRNA and also depends on p38 for its expression. In response to IL-1β, p38 MAP kinase hence represses the expression of E-selectin at the transcriptional and the post-transcriptional levels, via miR-146a and miR-31, respectively. These results highlight novel mechanisms by which p38 downregulates the expression of E-selectin through different microRNAs following inflammatory stimuli associated to cancer progression.Liang ZhongJacques HuotMartin J. SimardNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Liang Zhong Jacques Huot Martin J. Simard p38 activation induces production of miR-146a and miR-31 to repress E-selectin expression and inhibit transendothelial migration of colon cancer cells
description	Abstract Extravasation of circulating cancer cells determines their metastatic potential. This process is initiated by the adhesion of cancer cells to vascular endothelial cells through specific interactions between endothelial adhesion receptors such as E-selectin and their ligands on cancer cells. In the present study, we show that miR-146a and miR-181b impede the expression of E-selectin by repressing the activity of its transcription factor NF-κB, thereby impairing the metastatic potentials of colon cancer cells by decreasing their adhesion to, and migration through, the endothelium. Among the two microRNAs, only miR-146a is activated by IL-1β, through the activation of p38, ERK and JNK MAP kinases, as well as their downstream transcription factors GATA2, c-Fos and c-Jun. Inhibiting p38 MAP kinase increases NF-κB activity, at least partially via miR-146a. Inhibiting p38 also increases the expression of E-selectin at the post-transcriptional level via decreasing miR-31, which targets E-selectin mRNA and also depends on p38 for its expression. In response to IL-1β, p38 MAP kinase hence represses the expression of E-selectin at the transcriptional and the post-transcriptional levels, via miR-146a and miR-31, respectively. These results highlight novel mechanisms by which p38 downregulates the expression of E-selectin through different microRNAs following inflammatory stimuli associated to cancer progression.
format	article
author	Liang Zhong Jacques Huot Martin J. Simard
author_facet	Liang Zhong Jacques Huot Martin J. Simard
author_sort	Liang Zhong
title	p38 activation induces production of miR-146a and miR-31 to repress E-selectin expression and inhibit transendothelial migration of colon cancer cells
title_short	p38 activation induces production of miR-146a and miR-31 to repress E-selectin expression and inhibit transendothelial migration of colon cancer cells
title_full	p38 activation induces production of miR-146a and miR-31 to repress E-selectin expression and inhibit transendothelial migration of colon cancer cells
title_fullStr	p38 activation induces production of miR-146a and miR-31 to repress E-selectin expression and inhibit transendothelial migration of colon cancer cells
title_full_unstemmed	p38 activation induces production of miR-146a and miR-31 to repress E-selectin expression and inhibit transendothelial migration of colon cancer cells
title_sort	p38 activation induces production of mir-146a and mir-31 to repress e-selectin expression and inhibit transendothelial migration of colon cancer cells
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/f2e4ef41a8f84b8cad6220c1adb09894
work_keys_str_mv	AT liangzhong p38activationinducesproductionofmir146aandmir31torepresseselectinexpressionandinhibittransendothelialmigrationofcoloncancercells AT jacqueshuot p38activationinducesproductionofmir146aandmir31torepresseselectinexpressionandinhibittransendothelialmigrationofcoloncancercells AT martinjsimard p38activationinducesproductionofmir146aandmir31torepresseselectinexpressionandinhibittransendothelialmigrationofcoloncancercells
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p38 activation induces production of miR-146a and miR-31 to repress E-selectin expression and inhibit transendothelial migration of colon cancer cells

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