ZNF703 promotes tumor progression in ovarian cancer by interacting with HE4 and epigenetically regulating PEA15
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(2020) 39:264
RESEARCH
Open Access
ZNF703 promotes tumor progression in ovarian cancer by interacting with HE4 and epigenetically regulating PEA15 Shuang Wang1,2, Caixia Wang3, Yuexin Hu1,2, Xiao Li1,2, Shan Jin4, Ouxuan Liu1,2, Rui Gou1,2, Yuan Zhuang1,2, Qian Guo1,2, Xin Nie1,2, Liancheng Zhu1,2, Juanjuan Liu1,2 and Bei Lin1,2*
Abstract Background: It is known that the transcription factor zinc finger protein 703 (ZNF703) plays an important role in physiological functions and the occurrence and development of various tumors. However, the role and mechanism of ZNF703 in ovarian cancer are unclear. Materials and methods: Immunohistochemistry was used to analyze the expression of ZNF703 in ovarian cancer patients and to assess the effect of ZNF703 expression on the survival and prognosis of ovarian cancer patients. ZNF703 overexpression and suppression expression experiments were used to evaluate the effect of ZNF703 on malignant biological behavior of ovarian cancer cells in vitro. Detecting the interaction between HE4 and ZNF703 by immunofluorescence colocalization and coprecipitation, and nuclear translocation. Chromatin immunoprecipitation-sequencing (ChIP-Seq), dual luciferase reporter assay, ChIP-PCR, in vivo model were applied to study the molecular mechanism of ZNF703 affecting the development of ovarian cancer. Results: ZNF703 was highly expressed in ovarian cancer tissues, and its expression level is related to the prognosis of ovarian cancer patients. In vivo and in vitro experiments confirmed that ZNF703 overexpression/inhibition expression will promoted/inhibited the malignant biological behavior of ovarian cancer. Mechanically, ZNF703 interacted with HE4, and HE4 promoted nuclear translocation of ZNF703. ChIP-Seq identified multiple regulatory targets of ZNF703, of which ZNF703 directly binds to the enhancer region of PEA15 to promote the transcription of PEA15 and thereby promoted the proliferation of cancer cells. Conclusion: The results showed that ZNF703 as an oncogene played an important role in the epigenetic modification of ovarian cancer proliferation, and suggested that ZNF703 as a transcription factor may become a prognostic factor and a potential therapeutic target for ovarian cancer. Keywords: Ovarian cancer, ZNF703, HE4, PEA15, ChIP-Seq
* Correspondence: [email protected] 1 Department of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical University, No. 36, Sanhao Street, Heping District, Liaoning, Shenyang 110004, People’s Republic of China 2 Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shenyang, Liaoning, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original auth
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