Open Access

ARTICLE

Demethylation of Repressor Element-1 Silencing Transcription (REST) Suppresses the Malignant Phenotype of Breast Cancer via MMP9

Ying Liu^*†, Hui Lv^‡, Xiaoying Wu^*§, Jun Zhou^¶, Ying Shi^#, Jifang Wen^*†

* Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
† Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, P.R. China
‡ University of Colorado Denver, Aurora, CO, USA
§ Department of Medical Ultrastructure, School of Basic Medical Sciences, Central South University, Changsha, Hunan, P.R. China
¶ Institute of Pathology, Department of Pathology, Xiangnan University, Chenzhou, Hunan, P.R. China
# Department of Pathology and Pathophysiology, Xiamen Medical College, Fujian, P.R. China

Oncology Research 2017, 25(3), 445-454. https://doi.org/10.3727/096504016X14747368729786

Abstract

Breast cancer is the leading cause of cancer deaths in females all over the world, mainly resulting from metastasis. Previous studies have revealed that repressor element-1 (RE-1) silencing transcription (REST) acted as a tumor suppressor in breast cancer. However, the mechanism by which REST is regulated remains unknown, and its role in the metastasis in breast cancer cells remains unclear. In the present study, we showed that the expression of REST was lower in breast cancer samples than that of adjacent samples by immunohistochemical analysis, which may be due to hypermethylation of the REST promoter. Low REST levels are significantly associated with malignant progression in breast cancer patients. Additionally, we elucidated the functions of REST on proliferation and invasion in breast cancer cells. Lentivirus transfection was used to overexpress REST in human breast MDA-MB-231 cells. Then the biologic consequences of overexpressing REST in regard to cell proliferation, apoptosis, and invasion were determined. Furthermore, we also determined matrix metalloproteinase-9 (MMP9) as a target of REST. These results demonstrate that downregulation of REST, a tumor suppressor in breast cancer, is associated with hypermethylation. Induced REST expression is capable of attenuating invasion ability of breast cancer cells, which may be a novel strategy for metastatic breast cancer treatment.

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