Oncotarget

Research Papers:

DNA methylation promotes paired box 2 expression via myeloid zinc finger 1 in endometrial cancer

Nan Jia, Jieyu Wang, Qing Li, Xiang Tao, Kaikai Chang, Keqin Hua, Yinhua Yu, Kwong-Kwok Wong and Weiwei Feng _

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Oncotarget. 2016; 7:84785-84797. https://doi.org/10.18632/oncotarget.12626

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Abstract

Nan Jia1,3,*, Jieyu Wang1,3,*, Qing Li1,3, Xiang Tao2, Kaikai Chang1,3, Keqin Hua1,3, Yinhua Yu3, Kwong-Kwok Wong4, Weiwei Feng1,3

1Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China

2Department of Pathology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China

3Shanghai Key Laboratory of Female Reproductive Endocrine-Related Disease, Fudan University, Shanghai, China

4Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

*These authors have contributed equally to this work

Correspondence to:

Weiwei Feng, email: wfeng7347@aliyun.com

Keywords: paired box 2, myeloid zinc finger 1, endometrial cancer, MassARRAY, DNA methylation

Received: April 05, 2016    Accepted: September 25, 2016    Published: October 13, 2016

ABSTRACT

This work investigated the role of paired box 2 (PAX2) in endometrial cancer and its epigenetic regulation mechanism. Endometrial cancer tissues and cell lines exhibited increased PAX2 expression compared with hyperplasia, normal endometrium and endometrial epithelial cells. Knock-down of PAX2 resulted in reduced cell viability, invasion and migration, and PAX2 overexpression caused the opposite effects. Increased methylation of the PAX2 promoter was observed in both cancer tissues and cell lines and was positively correlated with PAX2 expression. After 5-Aza-CdR treatment, PAX2 mRNA and protein were down-regulated, and PAX2 methylation was decreased. Deletion analysis confirmed that a repressive transcriptional regulatory region of the PAX2 promoter coincided with the hypermethylated region identified in MassARRAY analysis. Binding sites of myeloid zinc finger 1 (MZF1) are predicted in the defined region. Knock-down of MZF1 up-regulated the transcriptional activity and protein level of PAX2 after 5-Aza-CdR treatment, which indicated that MZF1 may act as a repressive transcription factor when the PAX2 promoter is unmethylated. In conclusion, PAX2 is involved in the carcinogenesis of endometrial cancer by stimulating cell growth and promoting cell motility. The overexpression of PAX2 in endometrial cancer is regulated by promoter hypermethylation and the transcription factor MZF1.


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