Down-regulation of long non-coding RNA HOTAIR sensitizes breast cancer to trastuzumab

Abstract This study aimed to investigate the roles and possible molecular mechanisms of long non-coding RNA HOTAIR in regulating resistance to trastuzumab in breast cancer. Trastuzumab-resistant breast cancer cell line SK-BR-3-TR was assayed for the expression of HOX antisense intergenic RNA (HOTAIR...

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Autores principales:	Tianwen Chen, Zeming Liu, Wen Zeng, Tao Huang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3855a6244f2848df99e4664ad40a9a22
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spelling	oai:doaj.org-article:3855a6244f2848df99e4664ad40a9a222021-12-02T13:34:55ZDown-regulation of long non-coding RNA HOTAIR sensitizes breast cancer to trastuzumab10.1038/s41598-019-53699-w2045-2322https://doaj.org/article/3855a6244f2848df99e4664ad40a9a222019-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-53699-whttps://doaj.org/toc/2045-2322Abstract This study aimed to investigate the roles and possible molecular mechanisms of long non-coding RNA HOTAIR in regulating resistance to trastuzumab in breast cancer. Trastuzumab-resistant breast cancer cell line SK-BR-3-TR was assayed for the expression of HOX antisense intergenic RNA (HOTAIR), epithelial-mesenchymal transition (EMT)-related proteins or genes. Methylation levels of TGF- β, PTEN and cyclin-dependent kinase inhibitor 1B (or P27) were determined. In trastuzumab-resistant cell line, the mRNA level of HOTAIR was significantly up-regulated; in addition, the expression of TGF-β, Snail and Vimentin was also up-regulated, E-cadherin was down-regulated while the expression of HER2, PI3K, AKT, mTOR and MAPK in the HER2 receptor pathway and phosphorylation level of HER2 receptor remained unchanged, the methylation levels of the PTEN gene and TGF-β were increased and decreased, respectively. RNA interference downregulated the HOTAIR level and sensitized the cells to trastuzumab. It also resulted in down-regulation of TGF-β, Snail, Vimentin, p-AKT, p-APK and CyclinD1 and up-regulation of E-cadherin, PTEN and P27. Besides, the methylation levels of the PTEN gene and TGF-β were reduced and increased, respectively. Mouse models grafted with SK-BR-3-TR grew faster than with SK-BR-3-TS and siHOTAIR-SK-BR-3-TR.Tianwen ChenZeming LiuWen ZengTao HuangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tianwen Chen Zeming Liu Wen Zeng Tao Huang Down-regulation of long non-coding RNA HOTAIR sensitizes breast cancer to trastuzumab
description	Abstract This study aimed to investigate the roles and possible molecular mechanisms of long non-coding RNA HOTAIR in regulating resistance to trastuzumab in breast cancer. Trastuzumab-resistant breast cancer cell line SK-BR-3-TR was assayed for the expression of HOX antisense intergenic RNA (HOTAIR), epithelial-mesenchymal transition (EMT)-related proteins or genes. Methylation levels of TGF- β, PTEN and cyclin-dependent kinase inhibitor 1B (or P27) were determined. In trastuzumab-resistant cell line, the mRNA level of HOTAIR was significantly up-regulated; in addition, the expression of TGF-β, Snail and Vimentin was also up-regulated, E-cadherin was down-regulated while the expression of HER2, PI3K, AKT, mTOR and MAPK in the HER2 receptor pathway and phosphorylation level of HER2 receptor remained unchanged, the methylation levels of the PTEN gene and TGF-β were increased and decreased, respectively. RNA interference downregulated the HOTAIR level and sensitized the cells to trastuzumab. It also resulted in down-regulation of TGF-β, Snail, Vimentin, p-AKT, p-APK and CyclinD1 and up-regulation of E-cadherin, PTEN and P27. Besides, the methylation levels of the PTEN gene and TGF-β were reduced and increased, respectively. Mouse models grafted with SK-BR-3-TR grew faster than with SK-BR-3-TS and siHOTAIR-SK-BR-3-TR.
format	article
author	Tianwen Chen Zeming Liu Wen Zeng Tao Huang
author_facet	Tianwen Chen Zeming Liu Wen Zeng Tao Huang
author_sort	Tianwen Chen
title	Down-regulation of long non-coding RNA HOTAIR sensitizes breast cancer to trastuzumab
title_short	Down-regulation of long non-coding RNA HOTAIR sensitizes breast cancer to trastuzumab
title_full	Down-regulation of long non-coding RNA HOTAIR sensitizes breast cancer to trastuzumab
title_fullStr	Down-regulation of long non-coding RNA HOTAIR sensitizes breast cancer to trastuzumab
title_full_unstemmed	Down-regulation of long non-coding RNA HOTAIR sensitizes breast cancer to trastuzumab
title_sort	down-regulation of long non-coding rna hotair sensitizes breast cancer to trastuzumab
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/3855a6244f2848df99e4664ad40a9a22
work_keys_str_mv	AT tianwenchen downregulationoflongnoncodingrnahotairsensitizesbreastcancertotrastuzumab AT zemingliu downregulationoflongnoncodingrnahotairsensitizesbreastcancertotrastuzumab AT wenzeng downregulationoflongnoncodingrnahotairsensitizesbreastcancertotrastuzumab AT taohuang downregulationoflongnoncodingrnahotairsensitizesbreastcancertotrastuzumab
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Down-regulation of long non-coding RNA HOTAIR sensitizes breast cancer to trastuzumab

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