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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00220

IRF6 is directly regulated by ZEB1 and ELF3, and predicts a favorable prognosis in gastric cancer

Dandan Li1, Ping Cheng2,  Jingjie Wang1, Xuemei Qiu1, Xudong Zhang1, Li Xu1,  Ying Liu1* and  Shanshan Qin1*
  • 1Hubei University of Medicine, China
  • 2Shiyan Hospital of Traditional Chinese Medicine, China

Interferon regulatory factor 6 (IRF6) acts as a tumor suppressor and controls cell differentiation in ectodermal and craniofacial tissues by regulating expression of target genes. However, its function in gastric cancer (GC) remains unknown to date. In this study, we found that the IRF6 expression was significantly downregulated in GC. And the decreased expression of IRF6 was clinically correlated with poor prognosis of GC. Moreover, loss-of-function and gain-of-function studies showed that IRF6 was negatively regulated by ZEB1 but positively regulated by ELF3. Additionally, transcription factor ZEB1 and ELF3 could directly bind on IRF6 promoter, which suggested that transcription factor IRF6 is transcriptionally regulated by ZEB1 and ELF3. Nevertheless, we found that IRF6 expression was negatively related to its promoter methylation in TCGA stomach cancer cohorts. The downregulation of IRF6 in GC might be due to the overexpression of ZEB1 and the DNA methylation of IRF6 promoter.

Keywords: IRF6, Zeb1, ELF3, Transcriptional regulation, gastric cancer

Received: 09 Jul 2018; Accepted: 12 Mar 2019.

Edited by:

Rupert Langer, University of Bern, Switzerland

Reviewed by:

Toru Furukawa, School of Medicine, Tohoku University, Japan
Jens Neumann, Ludwig Maximilian University of Munich, Germany  

Copyright: © 2019 Li, Cheng, Wang, Qiu, Zhang, Xu, Liu and Qin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Ying Liu, Hubei University of Medicine, Shiyan, Hubei, China,
Dr. Shanshan Qin, Hubei University of Medicine, Shiyan, Hubei, China,