DNA methylation promotes paired box 2 expression via myeloid zinc finger 1 in endometrial cancer
Metrics: PDF 1581 views | HTML 1874 views | ?
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
Weiwei Feng, email: [email protected]
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
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.