Trichostatin A Suppresses EGFR Expression through Induction of MicroRNA-7 in an HDAC-Independent Manner in Lapatinib-Treated Cells

Lapatinib, a dual EGFR/HER2 tyrosine kinase inhibitor, has been shown to improve the survival rate of patients with advanced HER2-positive breast cancers. However, the off-target activity of lapatinib in inducing EGFR expression without tyrosine kinase activity was demonstrated to render HER2-negati...

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Main Authors:	Tu, Chih-Yen, Chen, Chia-Hung, Hsia, Te-Chun, Hsu, Min-Hsiang, Wei, Ya-Ling, Yu, Meng-Chieh, Chen, Wen-Shu, Hsu, Ke-Wei, Yeh, Ming-Hsin, Liu, Liang-Chih, Chen, Yun-Ju, Huang, Wei-Chien
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950925/

id	pubmed-3950925
recordtype	oai_dc
spelling	pubmed-39509252014-04-06 Trichostatin A Suppresses EGFR Expression through Induction of MicroRNA-7 in an HDAC-Independent Manner in Lapatinib-Treated Cells Tu, Chih-Yen Chen, Chia-Hung Hsia, Te-Chun Hsu, Min-Hsiang Wei, Ya-Ling Yu, Meng-Chieh Chen, Wen-Shu Hsu, Ke-Wei Yeh, Ming-Hsin Liu, Liang-Chih Chen, Yun-Ju Huang, Wei-Chien Research Article Lapatinib, a dual EGFR/HER2 tyrosine kinase inhibitor, has been shown to improve the survival rate of patients with advanced HER2-positive breast cancers. However, the off-target activity of lapatinib in inducing EGFR expression without tyrosine kinase activity was demonstrated to render HER2-negative breast cancer cells more metastatic, suggesting a limitation to the therapeutic effectiveness of this dual inhibitor in HER2-heterogeneous tumors. Therefore, targeting EGFR expression may be a feasible approach to improve the anticancer efficiency of lapatinib-based therapy. Inhibition of HDAC has been previously reported to epigenetically suppress EGFR protein expression. In this study, however, our data indicated that treatment with HDAC inhibitors trichostatin A (TSA), but not suberoylanilide hydroxamic acid (SAHA) or HDAC siRNA, can attenuate both protein and mRNA expressions of EGFR in lapatinib-treated triple-negative breast cancer cells, suggesting that TSA may suppress EGFR expression independently of HDAC inhibition. Nevertheless, TSA reduced EGFR 3′UTR activity and induced the gene expression of microRNA-7, a known EGFR-targeting microRNA. Furthermore, treatment with microRNA-7 inhibitor attenuated TSA-mediated EGFR suppression. These results suggest that TSA induced microRNA-7 expression to downregulate EGFR expression in an HDAC-independent manner. Hindawi Publishing Corporation 2014 2014-02-23 /pmc/articles/PMC3950925/ /pubmed/24707474 http://dx.doi.org/10.1155/2014/168949 Text en Copyright © 2014 Chih-Yen Tu et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Tu, Chih-Yen Chen, Chia-Hung Hsia, Te-Chun Hsu, Min-Hsiang Wei, Ya-Ling Yu, Meng-Chieh Chen, Wen-Shu Hsu, Ke-Wei Yeh, Ming-Hsin Liu, Liang-Chih Chen, Yun-Ju Huang, Wei-Chien
spellingShingle	Tu, Chih-Yen Chen, Chia-Hung Hsia, Te-Chun Hsu, Min-Hsiang Wei, Ya-Ling Yu, Meng-Chieh Chen, Wen-Shu Hsu, Ke-Wei Yeh, Ming-Hsin Liu, Liang-Chih Chen, Yun-Ju Huang, Wei-Chien Trichostatin A Suppresses EGFR Expression through Induction of MicroRNA-7 in an HDAC-Independent Manner in Lapatinib-Treated Cells
author_facet	Tu, Chih-Yen Chen, Chia-Hung Hsia, Te-Chun Hsu, Min-Hsiang Wei, Ya-Ling Yu, Meng-Chieh Chen, Wen-Shu Hsu, Ke-Wei Yeh, Ming-Hsin Liu, Liang-Chih Chen, Yun-Ju Huang, Wei-Chien
author_sort	Tu, Chih-Yen
title	Trichostatin A Suppresses EGFR Expression through Induction of MicroRNA-7 in an HDAC-Independent Manner in Lapatinib-Treated Cells
title_short	Trichostatin A Suppresses EGFR Expression through Induction of MicroRNA-7 in an HDAC-Independent Manner in Lapatinib-Treated Cells
title_full	Trichostatin A Suppresses EGFR Expression through Induction of MicroRNA-7 in an HDAC-Independent Manner in Lapatinib-Treated Cells
title_fullStr	Trichostatin A Suppresses EGFR Expression through Induction of MicroRNA-7 in an HDAC-Independent Manner in Lapatinib-Treated Cells
title_full_unstemmed	Trichostatin A Suppresses EGFR Expression through Induction of MicroRNA-7 in an HDAC-Independent Manner in Lapatinib-Treated Cells
title_sort	trichostatin a suppresses egfr expression through induction of microrna-7 in an hdac-independent manner in lapatinib-treated cells
description	Lapatinib, a dual EGFR/HER2 tyrosine kinase inhibitor, has been shown to improve the survival rate of patients with advanced HER2-positive breast cancers. However, the off-target activity of lapatinib in inducing EGFR expression without tyrosine kinase activity was demonstrated to render HER2-negative breast cancer cells more metastatic, suggesting a limitation to the therapeutic effectiveness of this dual inhibitor in HER2-heterogeneous tumors. Therefore, targeting EGFR expression may be a feasible approach to improve the anticancer efficiency of lapatinib-based therapy. Inhibition of HDAC has been previously reported to epigenetically suppress EGFR protein expression. In this study, however, our data indicated that treatment with HDAC inhibitors trichostatin A (TSA), but not suberoylanilide hydroxamic acid (SAHA) or HDAC siRNA, can attenuate both protein and mRNA expressions of EGFR in lapatinib-treated triple-negative breast cancer cells, suggesting that TSA may suppress EGFR expression independently of HDAC inhibition. Nevertheless, TSA reduced EGFR 3′UTR activity and induced the gene expression of microRNA-7, a known EGFR-targeting microRNA. Furthermore, treatment with microRNA-7 inhibitor attenuated TSA-mediated EGFR suppression. These results suggest that TSA induced microRNA-7 expression to downregulate EGFR expression in an HDAC-independent manner.
publisher	Hindawi Publishing Corporation
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950925/
_version_	1612066818188378112

Trichostatin A Suppresses EGFR Expression through Induction of MicroRNA-7 in an HDAC-Independent Manner in Lapatinib-Treated Cells

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