miR-19a contributes to gefitinib resistance and epithelial mesenchymal transition in non-small cell lung cancer cells by targeting c-Met

Abstract Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is used as a first-line treatment for advanced non-small cell lung cancer (NSCLC). However, most NSCLC patients inevitably develop gefitinib resistance, and the mechanisms underlying this resistance are not ful...

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Autores principales:	Xiaonian Cao, Senyan Lai, Fayong Hu, Guodong Li, Guihua Wang, Xuelai Luo, Xiangning Fu, Junbo Hu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dccf75983d65414cbb460bcafeecbc54
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spelling	oai:doaj.org-article:dccf75983d65414cbb460bcafeecbc542021-12-02T16:06:58ZmiR-19a contributes to gefitinib resistance and epithelial mesenchymal transition in non-small cell lung cancer cells by targeting c-Met10.1038/s41598-017-01153-02045-2322https://doaj.org/article/dccf75983d65414cbb460bcafeecbc542017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01153-0https://doaj.org/toc/2045-2322Abstract Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is used as a first-line treatment for advanced non-small cell lung cancer (NSCLC). However, most NSCLC patients inevitably develop gefitinib resistance, and the mechanisms underlying this resistance are not fully understood. In this study, we show that miR-19a is significantly down-regulated in gefitinib-resistant NSCLC cell lines compared with gefitinib-sensitive cell lines. In addition, the down-regulation of miR-19a suppressed the expression of epithelial markers but induced the expression levels of mesenchymal markers. A mechanistic analysis revealed that miR-19a regulated c-Met expression by directly targeting the c-Met 3′UTR. Overexpression of miR-19a decreased c-Met expression and re-sensitized gefitinib-resistant NSCLC cells in vitro and in vivo. Consistent with the in vitro findings, the miR-19a serum level was significantly decreased in NSCLC patients with acquired gefitinib resistance compared with the level observed prior to the acquisition of resistance in each patient, indicating that miR-19a expression may be a valuable biomarker for the prediction of acquired gefitinib resistance in a clinical setting. Our data demonstrate that the miR-19a/c-Met pathway plays a critical role in acquired resistance to gefitinib and that the manipulation of miR-19a might provide a therapeutic strategy for overcoming acquired gefitinib resistance.Xiaonian CaoSenyan LaiFayong HuGuodong LiGuihua WangXuelai LuoXiangning FuJunbo HuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaonian Cao Senyan Lai Fayong Hu Guodong Li Guihua Wang Xuelai Luo Xiangning Fu Junbo Hu miR-19a contributes to gefitinib resistance and epithelial mesenchymal transition in non-small cell lung cancer cells by targeting c-Met
description	Abstract Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is used as a first-line treatment for advanced non-small cell lung cancer (NSCLC). However, most NSCLC patients inevitably develop gefitinib resistance, and the mechanisms underlying this resistance are not fully understood. In this study, we show that miR-19a is significantly down-regulated in gefitinib-resistant NSCLC cell lines compared with gefitinib-sensitive cell lines. In addition, the down-regulation of miR-19a suppressed the expression of epithelial markers but induced the expression levels of mesenchymal markers. A mechanistic analysis revealed that miR-19a regulated c-Met expression by directly targeting the c-Met 3′UTR. Overexpression of miR-19a decreased c-Met expression and re-sensitized gefitinib-resistant NSCLC cells in vitro and in vivo. Consistent with the in vitro findings, the miR-19a serum level was significantly decreased in NSCLC patients with acquired gefitinib resistance compared with the level observed prior to the acquisition of resistance in each patient, indicating that miR-19a expression may be a valuable biomarker for the prediction of acquired gefitinib resistance in a clinical setting. Our data demonstrate that the miR-19a/c-Met pathway plays a critical role in acquired resistance to gefitinib and that the manipulation of miR-19a might provide a therapeutic strategy for overcoming acquired gefitinib resistance.
format	article
author	Xiaonian Cao Senyan Lai Fayong Hu Guodong Li Guihua Wang Xuelai Luo Xiangning Fu Junbo Hu
author_facet	Xiaonian Cao Senyan Lai Fayong Hu Guodong Li Guihua Wang Xuelai Luo Xiangning Fu Junbo Hu
author_sort	Xiaonian Cao
title	miR-19a contributes to gefitinib resistance and epithelial mesenchymal transition in non-small cell lung cancer cells by targeting c-Met
title_short	miR-19a contributes to gefitinib resistance and epithelial mesenchymal transition in non-small cell lung cancer cells by targeting c-Met
title_full	miR-19a contributes to gefitinib resistance and epithelial mesenchymal transition in non-small cell lung cancer cells by targeting c-Met
title_fullStr	miR-19a contributes to gefitinib resistance and epithelial mesenchymal transition in non-small cell lung cancer cells by targeting c-Met
title_full_unstemmed	miR-19a contributes to gefitinib resistance and epithelial mesenchymal transition in non-small cell lung cancer cells by targeting c-Met
title_sort	mir-19a contributes to gefitinib resistance and epithelial mesenchymal transition in non-small cell lung cancer cells by targeting c-met
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/dccf75983d65414cbb460bcafeecbc54
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miR-19a contributes to gefitinib resistance and epithelial mesenchymal transition in non-small cell lung cancer cells by targeting c-Met

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