Oncotarget

Research Papers:

Epigenetic repression of phosphatidylethanolamine N-methyltransferase (PEMT) in BRCA1-mutated breast cancer

Da Li, Fang-Fang Bi, Na-Na Chen, Ji-Min Cao, Wu-Ping Sun, Yi-Ming Zhou, Chen Cao, Chun-Yan Li and Qing Yang _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2014; 5:1315-1325. https://doi.org/10.18632/oncotarget.1800

Metrics: PDF 1132 views  |   HTML 1318 views  |   ?  


Abstract

Da Li1, Fang-Fang Bi1, Na-Na Chen2, Ji-Min Cao3, Wu-Ping Sun4, Yi-Ming Zhou4, Chen Cao5, Chun-Yan Li6, Qing Yang1

1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China

2 Department of Molecular Immunology, Graduate School of Medicine, Nagoya University, Nagoya, Japan

3 Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China

4 Division of Cell Signaling, National Institute for Physiological Sciences, Okazaki, Japan

5 Department of Pathology, Chinese PLA General Hospital, Beijing, China

6 Department of Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China

Correspondence:

Da Li, email:

Keywords: PEMT, DNA methylation, Histone modifications, BRCA1, Breast cancer

Received: January 27, 2014 Accepted:February 26, 2014 Published: February 27, 2014

Abstract

Phosphatidylethanolamine N-methyltransferase (PEMT) plays a critical role in breast cancer progression. However, the epigenetic mechanism regulating PEMT transcription remains largely unknown. Here, we show that the first promoter-specific transcript 1 is the major PEMT mRNA species, and methylation of the -132 site is a key regulatory element for the PEMT gene in BRCA1-mutated breast cancer. Mechanistically, hypermethylated -132 site-mediated loss of active histone marks H3K9ac and increase of repressive histone marks H3K9me enrichment synergistically inhibited PEMT transcription. Clinicopathological data indicated that a hypermethylated -132 site was associated with histological grade (P = 0.031) and estrogen receptor status (P = 0.004); univariate survival and multivariate analyses demonstrated that lymph node metastasis was an independent and reliable prognostic factor for BRCA1-mutated breast cancer patients. Our findings imply that genetic (e.g., BRCA1 mutation) and epigenetic mechanisms (e.g., DNA methylation and histone modifications) are jointly involved in the malignant progression of PEMT-related breast cancer.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 1800