BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma

Abstract Background: Bromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies. In this study, we aimed to explore the effect of BRD4 inhibition by JQ1 on in vitro cell growth, migration and invasion of salivary adenoid cystic carcinoma (SACC). Methods:...

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Autores principales: Wang,Limei, Wu,Xiuyin, Wang,Ruolin, Yang,Chengzhe, Li,Zhi, Wang,Cunwei, Zhang,Fenghe, Yang,Pishan
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2017
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Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602017000100213
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spelling oai:scielo:S0716-976020170001002132017-07-07BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinomaWang,LimeiWu,XiuyinWang,RuolinYang,ChengzheLi,ZhiWang,CunweiZhang,FengheYang,Pishan Salivary adenoid cystic carcinoma BRD4 inhibition Proliferation Migration Epithelial-mesenchymal transition Abstract Background: Bromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies. In this study, we aimed to explore the effect of BRD4 inhibition by JQ1 on in vitro cell growth, migration and invasion of salivary adenoid cystic carcinoma (SACC). Methods: The human normal epithelial cells and SACC cells (ACC-LM and ACC-83) were treated with JQ1 at concentrations of 0, 0.1, 0.5 or 1 μM. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Cell apoptosis and cell cycle distribution was evaluated by Flow cytometry. Immunofluorescence staining was used to examine the expression of BRD4 in SACC cells. The quantitative real-time polymerase chain reaction (qRT-PCR) assay and western blot assay were performed to examine messenger RNA (mRNA) and protein levels in SACC cells. Wound- healing assay and transwell assay were used to evaluate the activities of migration and invasion of SACC cells. Results: JQ1 exhibits no adverse effects on proliferation, cell cycle and cell apoptosis of the normal human epithelial cells, while suppressed proliferation and cell cycle, and induced apoptosis of SACC cells, down-regulated the mRNA and protein levels of BRD4 in SACC cells, meanwhile reduced protein expressions of c-myc and BCL-2, two known target genes of BRD4. Moreover, JQ1 inhibited SACC cell migration and invasion by regulating key epithelial-mesenchymal transition (EMT) characteristics including E-cadherin, Vimentin and Twist. Conclusions: BRD4 is an important transcription factor in SACC and BRD4 inhibition by JQ1 may be a new strategy for SACC treatment.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.50 20172017-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602017000100213en10.1186/s40659-017-0124-9
institution Scielo Chile
collection Scielo Chile
language English
topic Salivary adenoid cystic carcinoma
BRD4 inhibition
Proliferation
Migration
Epithelial-mesenchymal transition
spellingShingle Salivary adenoid cystic carcinoma
BRD4 inhibition
Proliferation
Migration
Epithelial-mesenchymal transition
Wang,Limei
Wu,Xiuyin
Wang,Ruolin
Yang,Chengzhe
Li,Zhi
Wang,Cunwei
Zhang,Fenghe
Yang,Pishan
BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
description Abstract Background: Bromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies. In this study, we aimed to explore the effect of BRD4 inhibition by JQ1 on in vitro cell growth, migration and invasion of salivary adenoid cystic carcinoma (SACC). Methods: The human normal epithelial cells and SACC cells (ACC-LM and ACC-83) were treated with JQ1 at concentrations of 0, 0.1, 0.5 or 1 μM. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Cell apoptosis and cell cycle distribution was evaluated by Flow cytometry. Immunofluorescence staining was used to examine the expression of BRD4 in SACC cells. The quantitative real-time polymerase chain reaction (qRT-PCR) assay and western blot assay were performed to examine messenger RNA (mRNA) and protein levels in SACC cells. Wound- healing assay and transwell assay were used to evaluate the activities of migration and invasion of SACC cells. Results: JQ1 exhibits no adverse effects on proliferation, cell cycle and cell apoptosis of the normal human epithelial cells, while suppressed proliferation and cell cycle, and induced apoptosis of SACC cells, down-regulated the mRNA and protein levels of BRD4 in SACC cells, meanwhile reduced protein expressions of c-myc and BCL-2, two known target genes of BRD4. Moreover, JQ1 inhibited SACC cell migration and invasion by regulating key epithelial-mesenchymal transition (EMT) characteristics including E-cadherin, Vimentin and Twist. Conclusions: BRD4 is an important transcription factor in SACC and BRD4 inhibition by JQ1 may be a new strategy for SACC treatment.
author Wang,Limei
Wu,Xiuyin
Wang,Ruolin
Yang,Chengzhe
Li,Zhi
Wang,Cunwei
Zhang,Fenghe
Yang,Pishan
author_facet Wang,Limei
Wu,Xiuyin
Wang,Ruolin
Yang,Chengzhe
Li,Zhi
Wang,Cunwei
Zhang,Fenghe
Yang,Pishan
author_sort Wang,Limei
title BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
title_short BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
title_full BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
title_fullStr BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
title_full_unstemmed BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
title_sort brd4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
publisher Sociedad de Biología de Chile
publishDate 2017
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602017000100213
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AT wuxiuyin brd4inhibitionsuppressescellgrowthmigrationandinvasionofsalivaryadenoidcysticcarcinoma
AT wangruolin brd4inhibitionsuppressescellgrowthmigrationandinvasionofsalivaryadenoidcysticcarcinoma
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AT zhangfenghe brd4inhibitionsuppressescellgrowthmigrationandinvasionofsalivaryadenoidcysticcarcinoma
AT yangpishan brd4inhibitionsuppressescellgrowthmigrationandinvasionofsalivaryadenoidcysticcarcinoma
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