title: Decreased expression of EZH2 reactivates RASSF2A by reversal of promoter methylation in breast cancer cells.
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.
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Maimaiti
authors.initials: M
authors.lastname: Yusufu
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Zeming
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Xingjie
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Thyroid and Breast Surgery, Wuhan Central Hospital, Wuhan, 430022, China.
authors.forename: Gongling
authors.initials: G
authors.lastname: Peng
authors.affiliation: Department of Thyroid and Breast Surgery, Wuhan Central Hospital, Wuhan, 430022, China.
authors.forename: Longqiang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Xiangwang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. lcp191@163.com.
authors.forename: Chunping
authors.initials: C
authors.lastname: Liu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D018899:CpG Islands; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis / Q000235:genetics; D019175:DNA Methylation; D015536:Down-Regulation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000964:Antimetabolites, Antineoplastic; C425300:RASSF2 protein, human; D025521:Tumor Suppressor Proteins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D001374:Azacitidine
keywords: EZH2; RASSF2A; methylation; tumor suppressor