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下调 GATA-1 可上调肺腺癌中的干扰素调节因子 3。

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

机构信息

Dpartment of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.

Department of Urology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.

出版信息

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

DOI:10.1038/s41598-017-02700-5
PMID:28566697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5451405/
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.

摘要

干扰素调节因子 3（IRF-3）通过激活干扰素系统，对病毒感染迅速做出反应而广为人知。我们之前曾报道过，E2F1、Sp1 和 Sp3 调节 IRF-3 的转录活性。最近，在肺癌中发现了 IRF-3 的不同表达模式，导致肿瘤发生中的免疫调节功能发生改变。然而，IRF-3 在肺癌中的转录调控机制尚未得到广泛研究。在这里，我们研究了 IRF-3 启动子的特征，发现 GATA-1 在体外和体内与 IRF-3 启动子的特定区域结合。我们在 Oncomine 数据库中发现，肺腺癌中存在升高的 IRF-3 和降低的 GATA-1 基因表达。此外，在人类肺腺癌中观察到更高的 IRF-3 基因表达，同时存在异常的 GATA-1 蛋白表达。我们进一步分析了肺腺癌细胞系中 GATA-1 和 IRF-3 表达的关系，发现通过 siRNA 抑制 GATA-1 可增加 IRF-3 的启动子活性、mRNA 和蛋白水平，而过表达 GATA-1 则下调 IRF-3 基因表达。总之，我们的结论是，在肺腺癌细胞中，GATA-1 的减少可能通过与 IRF-3 启动子的特定区域结合而上调 IRF-3。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5607/5451405/cf706645d63d/41598_2017_2700_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5607/5451405/194c1cd80aa0/41598_2017_2700_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5607/5451405/558ccb30cfbb/41598_2017_2700_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5607/5451405/e937c950ed8e/41598_2017_2700_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5607/5451405/6aab2fa2f4f3/41598_2017_2700_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5607/5451405/cf706645d63d/41598_2017_2700_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5607/5451405/194c1cd80aa0/41598_2017_2700_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5607/5451405/558ccb30cfbb/41598_2017_2700_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5607/5451405/e937c950ed8e/41598_2017_2700_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5607/5451405/6aab2fa2f4f3/41598_2017_2700_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5607/5451405/cf706645d63d/41598_2017_2700_Fig5_HTML.jpg

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