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Sci Rep. 2017 May 31;7(1):2551. doi: 10.1038/s41598-017-02700-5.

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

Author information

1
Dpartment of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
2
Department of Urology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
3
Dpartment of Pediatrics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, China.
4
Department of Pediatric Respiration, Affiliated Wuxi People's Hospital, Nanjing Medical University, Wuxi, Jiangsu Province, China.
5
Dpartment of Pediatrics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
6
Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University Vienna, Vienna, Austria.
7
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China. zhanghao@xzhmu.edu.cn.
8
Dpartment of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China. guopingzhou@aliyun.com.

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.

PMID:
28566697
PMCID:
PMC5451405
DOI:
10.1038/s41598-017-02700-5
[Indexed for MEDLINE]
Free PMC Article

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