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Cell Biol Int. 2016 Oct;40(10):1062-70. doi: 10.1002/cbin.10646. Epub 2016 Aug 3.

Decreased expression of EZH2 reactivates RASSF2A by reversal of promoter methylation in breast cancer cells.

Author information

1
Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
2
Department of Thyroid and Breast Surgery, Wuhan Central Hospital, Wuhan, 430022, China.
3
Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. lcp191@163.com.

Abstract

EZH2, the catalytic subunit of polycomb repressor complex 2, has oncogenic properties, whereas RASSF2A, a Ras association domain family protein, has a tumor suppressor role in many types of human cancer. However, the interrelationship between these two genes remains unclear. Here, we showed that the downregulation of EZH2 reduces CpG island methylation of the RASSF2A promoter, thereby leading to increased RASSF2A expression. Our findings also showed that knockdown of EZH2 increased RASSF2A expression in the human breast cancer cell line MCF-7 in cooperation with DNMT1. This was similar to the effect of 5-Aza-CdR, a DNA methylation inhibitor that reactivates tumor suppressor genes and activated RASSF2A expression in our study. The EZH2 inhibitor DZNep markedly suppressed the proliferation, migration, and invasion of MCF-7 cells treated with ADR and TAM. EZH2 inhibits the expression of tumor suppressor gene RASSF2A via promoter hypermethylation. Thus, it plays an important role in tumorigenesis and is a potential therapeutic target for the treatment of breast cancer.

KEYWORDS:

EZH2; RASSF2A; methylation; tumor suppressor

PMID:
27436059
DOI:
10.1002/cbin.10646
[Indexed for MEDLINE]

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