A microRNA signature of response to erlotinib is descriptive of TGFβ behaviour in NSCLC

Abstract Our previous work identified a 13-gene miRNA signature predictive of response to the epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in Non-Small Cell Lung Cancer cell lines. Bioinformatic analysis of the signature showed a functional convergence on TGFβ canonical signalling....

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Autores principales:	Madeline Krentz Gober, James P. Collard, Katherine Thompson, Esther P. Black
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/63a108947c5040c98b9e1ac1ac2632b6
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spelling	oai:doaj.org-article:63a108947c5040c98b9e1ac1ac2632b62021-12-02T12:30:54ZA microRNA signature of response to erlotinib is descriptive of TGFβ behaviour in NSCLC10.1038/s41598-017-04097-72045-2322https://doaj.org/article/63a108947c5040c98b9e1ac1ac2632b62017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04097-7https://doaj.org/toc/2045-2322Abstract Our previous work identified a 13-gene miRNA signature predictive of response to the epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in Non-Small Cell Lung Cancer cell lines. Bioinformatic analysis of the signature showed a functional convergence on TGFβ canonical signalling. We hypothesized that TGFβ signalling controls expression of the miRNA genes comprising an erlotinib response signature in NSCLC. Western analysis revealed that TGFβ signalling via Smad2/3/4 occurred differently between erlotinib-resistant A549 and erlotinib- sensitive PC9 cells. We showed that TGFβ induced an interaction between Smad4 and putative Smad Binding Elements in PC9. However, qRT-PCR analysis showed that endogenous miR-140/141/200c expression changes resulted from time in treatments, not the treatments themselves. Moreover, flow cytometry indicated that cells exited the cell cycle in the same manner. Taken together these data indicated that the miRNA comprising the signature are likely regulated by the cell cycle rather than by TGFβ. Importantly, this work revealed that TGFβ did not induce EMT in PC9 cells, but rather TGFβ-inhibition induced an EMT-intermediate. These data also show that growth/proliferation signals by constitutively-activated EGFR may rely on TGFβ and a possible relationship between TGFβ and EGFR signalling may prevent EMT progression in this context rather than promote it.Madeline Krentz GoberJames P. CollardKatherine ThompsonEsther P. BlackNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Madeline Krentz Gober James P. Collard Katherine Thompson Esther P. Black A microRNA signature of response to erlotinib is descriptive of TGFβ behaviour in NSCLC
description	Abstract Our previous work identified a 13-gene miRNA signature predictive of response to the epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in Non-Small Cell Lung Cancer cell lines. Bioinformatic analysis of the signature showed a functional convergence on TGFβ canonical signalling. We hypothesized that TGFβ signalling controls expression of the miRNA genes comprising an erlotinib response signature in NSCLC. Western analysis revealed that TGFβ signalling via Smad2/3/4 occurred differently between erlotinib-resistant A549 and erlotinib- sensitive PC9 cells. We showed that TGFβ induced an interaction between Smad4 and putative Smad Binding Elements in PC9. However, qRT-PCR analysis showed that endogenous miR-140/141/200c expression changes resulted from time in treatments, not the treatments themselves. Moreover, flow cytometry indicated that cells exited the cell cycle in the same manner. Taken together these data indicated that the miRNA comprising the signature are likely regulated by the cell cycle rather than by TGFβ. Importantly, this work revealed that TGFβ did not induce EMT in PC9 cells, but rather TGFβ-inhibition induced an EMT-intermediate. These data also show that growth/proliferation signals by constitutively-activated EGFR may rely on TGFβ and a possible relationship between TGFβ and EGFR signalling may prevent EMT progression in this context rather than promote it.
format	article
author	Madeline Krentz Gober James P. Collard Katherine Thompson Esther P. Black
author_facet	Madeline Krentz Gober James P. Collard Katherine Thompson Esther P. Black
author_sort	Madeline Krentz Gober
title	A microRNA signature of response to erlotinib is descriptive of TGFβ behaviour in NSCLC
title_short	A microRNA signature of response to erlotinib is descriptive of TGFβ behaviour in NSCLC
title_full	A microRNA signature of response to erlotinib is descriptive of TGFβ behaviour in NSCLC
title_fullStr	A microRNA signature of response to erlotinib is descriptive of TGFβ behaviour in NSCLC
title_full_unstemmed	A microRNA signature of response to erlotinib is descriptive of TGFβ behaviour in NSCLC
title_sort	microrna signature of response to erlotinib is descriptive of tgfβ behaviour in nsclc
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/63a108947c5040c98b9e1ac1ac2632b6
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A microRNA signature of response to erlotinib is descriptive of TGFβ behaviour in NSCLC

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