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EZH2 overexpression dampens tumor-suppressive signals via an EGR1 silencer to drive breast tumorigenesis
Guan,Xiaowen1,2,3; Deng,Houliang1,2,3; Choi,Un Lam1,2,3; Li,Zhengfeng1,2,3; Yang,Yiqi1,2,3; Zeng,Jianming1,2,3; Liu,Yunze1,2,3; Zhang,Xuanjun1,2,3; Li,Gang1,2,3
2020-11-26
Source PublicationOncogene
ISSN0950-9232
Volume39Issue:48Pages:7127-7141
Abstract

The mechanism underlying EZH2 overexpression in breast cancer and its involvement in tumorigenesis remain poorly understood. In this study, we developed an approach to systematically identify the trans-acting factors regulating the EZH2 expression, and identified more than 20 such factors. We revealed reciprocal regulation of early growth response 1 (EGR1) and EZH2: EGR1 activates the expression of EZH2, and EZH2 represses EGR1 expression. Using CRISPR-mediated genome/epigenome editing, we demonstrated that EHZ2 represses EGR1 expression through a silencer downstream of the EGR1 gene. Deletion of the EGR1 silencer resulted in reduced cell growth, invasion, tumorigenicity of breast cancer cells, and extensive changes in gene expression, such as upregulation of GADD45, DDIT3, and RND1; and downregulation of genes encoding cholesterol biosynthesis pathway enzymes. We hypothesize that EZH2/PRC2 acts as a “brake” for EGR1 expression by targeting the EGR1 silencer, and EZH2 overexpression dampens tumor-suppressive signals mediated by EGR1 to drive breast tumorigenesis.

DOI10.1038/s41388-020-01484-9
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaBiochemistry & Molecular Biology ; Oncology ; Genetics & Heredity ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
WOS IDWOS:000574731000002
Scopus ID2-s2.0-85091740216
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorLi,Gang
Affiliation1.Faculty of Health Sciences,University of Macau,Macao
2.Cancer Centre,Faculty of Health Sciences,University of Macau,Macao
3.Centre of Reproduction,Development and Aging,Institute of Translational Medicine,Faculty of Health Sciences,University of Macau,Macao
First Author AffilicationFaculty of Health Sciences;  Cancer Centre
Corresponding Author AffilicationFaculty of Health Sciences;  Cancer Centre
Recommended Citation
GB/T 7714
Guan,Xiaowen,Deng,Houliang,Choi,Un Lam,et al. EZH2 overexpression dampens tumor-suppressive signals via an EGR1 silencer to drive breast tumorigenesis[J]. Oncogene,2020,39(48):7127-7141.
APA Guan,Xiaowen,Deng,Houliang,Choi,Un Lam,Li,Zhengfeng,Yang,Yiqi,Zeng,Jianming,Liu,Yunze,Zhang,Xuanjun,&Li,Gang.(2020).EZH2 overexpression dampens tumor-suppressive signals via an EGR1 silencer to drive breast tumorigenesis.Oncogene,39(48),7127-7141.
MLA Guan,Xiaowen,et al."EZH2 overexpression dampens tumor-suppressive signals via an EGR1 silencer to drive breast tumorigenesis".Oncogene 39.48(2020):7127-7141.
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