Down-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma

Abstract Interferon regulatory factor 3 (IRF-3) is widely known for its prompt response against viral infection by activating the interferon system. We previously reported that E2F1, Sp1 and Sp3 regulated transcriptional activity of IRF-3. Recently, different expression patterns of IRF-3 were found...

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Autores principales:	Lu-Lu Wang, Zheng-Sen Chen, Wen-Di Zhou, Jin Shu, Xiao-Hua Wang, Rui Jin, Li-Li Zhuang, Mir Alireza Hoda, Hao Zhang, Guo-Ping Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78772c5eb2534f93aca2ace855ee5bab
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spelling	oai:doaj.org-article:78772c5eb2534f93aca2ace855ee5bab2021-12-02T12:30:52ZDown-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma10.1038/s41598-017-02700-52045-2322https://doaj.org/article/78772c5eb2534f93aca2ace855ee5bab2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02700-5https://doaj.org/toc/2045-2322Abstract Interferon regulatory factor 3 (IRF-3) is widely known for its prompt response against viral infection by activating the interferon system. We previously reported that E2F1, Sp1 and Sp3 regulated transcriptional activity of IRF-3. Recently, different expression patterns of IRF-3 were found in lung cancer, leading to the alternation of the immunomodulatory function in tumorigenesis. However, the mechanism of transcriptional regulation of IRF-3 in lung cancer has not been extensively studied. Here, we investigated the characterization of IRF-3 promoter and found that GATA-1 bound to a specific domain of IRF-3 promoter in vitro and in vivo. We found elevated IRF-3 and decreased GATA-1 gene expression in lung adenocarcinoma in Oncomine database. Additionally, higher IRF-3 gene expression was observed in human lung adenocarcinoma, accompanied by aberrant GATA-1 protein expression. We further analyzed the relationship of GATA-1 and IRF-3 expression in lung adenocarcinoma cell lines and found that inhibition of GATA-1 by siRNA increased the promoter activity, mRNA and protein levels of IRF-3, while over-expression of GATA-1 down-regulated IRF-3 gene expression. Taken together, we conclude that reduced GATA-1 could be responsible for the upregulation of IRF-3 in lung adenocarcinoma cells through binding with a specific domain of IRF-3 promoter.Lu-Lu WangZheng-Sen ChenWen-Di ZhouJin ShuXiao-Hua WangRui JinLi-Li ZhuangMir Alireza HodaHao ZhangGuo-Ping ZhouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lu-Lu Wang Zheng-Sen Chen Wen-Di Zhou Jin Shu Xiao-Hua Wang Rui Jin Li-Li Zhuang Mir Alireza Hoda Hao Zhang Guo-Ping Zhou Down-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma
description	Abstract Interferon regulatory factor 3 (IRF-3) is widely known for its prompt response against viral infection by activating the interferon system. We previously reported that E2F1, Sp1 and Sp3 regulated transcriptional activity of IRF-3. Recently, different expression patterns of IRF-3 were found in lung cancer, leading to the alternation of the immunomodulatory function in tumorigenesis. However, the mechanism of transcriptional regulation of IRF-3 in lung cancer has not been extensively studied. Here, we investigated the characterization of IRF-3 promoter and found that GATA-1 bound to a specific domain of IRF-3 promoter in vitro and in vivo. We found elevated IRF-3 and decreased GATA-1 gene expression in lung adenocarcinoma in Oncomine database. Additionally, higher IRF-3 gene expression was observed in human lung adenocarcinoma, accompanied by aberrant GATA-1 protein expression. We further analyzed the relationship of GATA-1 and IRF-3 expression in lung adenocarcinoma cell lines and found that inhibition of GATA-1 by siRNA increased the promoter activity, mRNA and protein levels of IRF-3, while over-expression of GATA-1 down-regulated IRF-3 gene expression. Taken together, we conclude that reduced GATA-1 could be responsible for the upregulation of IRF-3 in lung adenocarcinoma cells through binding with a specific domain of IRF-3 promoter.
format	article
author	Lu-Lu Wang Zheng-Sen Chen Wen-Di Zhou Jin Shu Xiao-Hua Wang Rui Jin Li-Li Zhuang Mir Alireza Hoda Hao Zhang Guo-Ping Zhou
author_facet	Lu-Lu Wang Zheng-Sen Chen Wen-Di Zhou Jin Shu Xiao-Hua Wang Rui Jin Li-Li Zhuang Mir Alireza Hoda Hao Zhang Guo-Ping Zhou
author_sort	Lu-Lu Wang
title	Down-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma
title_short	Down-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma
title_full	Down-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma
title_fullStr	Down-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma
title_full_unstemmed	Down-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma
title_sort	down-regulated gata-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/78772c5eb2534f93aca2ace855ee5bab
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_version_	1718394286623424512

Down-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma

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