Down-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma.
Down-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma.
复制标题
肺腺癌中下调的 GATA-1 上调干扰素调节因子 3
DOI：
10.1038/s41598-017-02700-5
复制
发表时间：
2017-05-31
影响因子：
4.6
通讯作者：
Zhou GP
中科院分区：
文献类型：
--
作者：
Wang LL;Chen ZS;Zhou WD;Shu J;Wang XH;Jin R;Zhuang LL;Hoda MA;Zhang H;Zhou GP
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.
