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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 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.

SUBMITTER: Wang LL 

PROVIDER: S-EPMC5451405 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Wang Lu-Lu LL   Chen Zheng-Sen ZS   Zhou Wen-Di WD   Shu Jin J   Wang Xiao-Hua XH   Jin Rui R   Zhuang Li-Li LL   Hoda Mir Alireza MA   Zhang Hao H   Zhou Guo-Ping GP  

Scientific reports 20170531 1


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  ...[more]

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