BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent and poorly responsive cancers worldwide. Bromodomain and extraterminal (BET) inhibitors, such as JQ1 and OTX-015, inhibit BET protein binding to acetylated residues in histones. However, the physiological mechanisms and regulatory...

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Autores principales:	Hae In Choi, Ga Yeong An, Mina Baek, Eunyoung Yoo, Jin Choul Chai, Young Seek Lee, Kyoung Hwa Jung, Young Gyu Chai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2bf925a7b1f44275898bb8e721a341c7
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spelling	oai:doaj.org-article:2bf925a7b1f44275898bb8e721a341c72021-12-02T15:57:03ZBET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA410.1038/s41598-021-91284-22045-2322https://doaj.org/article/2bf925a7b1f44275898bb8e721a341c72021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91284-2https://doaj.org/toc/2045-2322Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent and poorly responsive cancers worldwide. Bromodomain and extraterminal (BET) inhibitors, such as JQ1 and OTX-015, inhibit BET protein binding to acetylated residues in histones. However, the physiological mechanisms and regulatory processes of BET inhibition in HCC remain unclear. To explore BET inhibitors’ potential role in the molecular mechanisms underlying their anticancer effects in HCC, we analyzed BET inhibitor-treated HCC cells’ gene expression profiles with RNA-seq and bioinformatics analysis. BET inhibitor treatment significantly downregulated genes related to bromodomain-containing proteins 4 (BRD4), such as ACSL5, SLC38A5, and ICAM2. Importantly, some cell migration-related genes, including AOC3, CCR6, SSTR5, and SCL7A11, were significantly downregulated. Additionally, bioinformatics analysis using Ingenuity Knowledge Base Ingenuity Pathway Analysis (IPA) revealed that SMARCA4 regulated migration response molecules. Furthermore, knockdown of SMARCA4 gene expression by siRNA treatment significantly reduced cell migration and the expression of migration-related genes. In summary, our results indicated that BET inhibitor treatment in HCC cell lines reduces cell migration through the downregulation of SMARCA4.Hae In ChoiGa Yeong AnMina BaekEunyoung YooJin Choul ChaiYoung Seek LeeKyoung Hwa JungYoung Gyu ChaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hae In Choi Ga Yeong An Mina Baek Eunyoung Yoo Jin Choul Chai Young Seek Lee Kyoung Hwa Jung Young Gyu Chai BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4
description	Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent and poorly responsive cancers worldwide. Bromodomain and extraterminal (BET) inhibitors, such as JQ1 and OTX-015, inhibit BET protein binding to acetylated residues in histones. However, the physiological mechanisms and regulatory processes of BET inhibition in HCC remain unclear. To explore BET inhibitors’ potential role in the molecular mechanisms underlying their anticancer effects in HCC, we analyzed BET inhibitor-treated HCC cells’ gene expression profiles with RNA-seq and bioinformatics analysis. BET inhibitor treatment significantly downregulated genes related to bromodomain-containing proteins 4 (BRD4), such as ACSL5, SLC38A5, and ICAM2. Importantly, some cell migration-related genes, including AOC3, CCR6, SSTR5, and SCL7A11, were significantly downregulated. Additionally, bioinformatics analysis using Ingenuity Knowledge Base Ingenuity Pathway Analysis (IPA) revealed that SMARCA4 regulated migration response molecules. Furthermore, knockdown of SMARCA4 gene expression by siRNA treatment significantly reduced cell migration and the expression of migration-related genes. In summary, our results indicated that BET inhibitor treatment in HCC cell lines reduces cell migration through the downregulation of SMARCA4.
format	article
author	Hae In Choi Ga Yeong An Mina Baek Eunyoung Yoo Jin Choul Chai Young Seek Lee Kyoung Hwa Jung Young Gyu Chai
author_facet	Hae In Choi Ga Yeong An Mina Baek Eunyoung Yoo Jin Choul Chai Young Seek Lee Kyoung Hwa Jung Young Gyu Chai
author_sort	Hae In Choi
title	BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4
title_short	BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4
title_full	BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4
title_fullStr	BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4
title_full_unstemmed	BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4
title_sort	bet inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting smarca4
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2bf925a7b1f44275898bb8e721a341c7
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BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4

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