ERα promotes transcription of tumor suppressor gene ApoA-I by establishing H3K27ac-enriched chromatin microenvironment in breast cancer cells  

作　　者：Bingjie WANG Yinghui SHEN Tianyu LIU Li TAN 

机构地区：[1]Center for Medical Research and Innovation,Shanghai Pudong Hospital,Fudan University Pudong Medical Center,and Shanghai Key Laboratory of Medical Epigenetics,Institutes of Biomedical Sciences,Fucian University,Shanghai 200032,China [2]Colorectal Cancer Center,Department of General Surgery,Zhongshan Hospital,Fudan University,Shanghai 200032,China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2021年第12期1034-1044,共11页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：supported by the National Natural Science Foundation of China(Nos.81672785,31871291,and82073113 to Li TAN);the National Key R&D Project of China(No.2016YFA0101800 to Li TAN);supported by the Innovative Research Team of High-level Local University in Shanghai。

摘　　要：Apolipoprotein A-I(Apo A-I),the main protein component of high-density lipoprotein(HDL),plays a pivotal role in reverse cholesterol transport(RCT).Previous studies indicated a reduction of serum Apo A-I levels in various types of cancer,suggesting Apo A-I as a potential cancer biomarker.Herein,ectopically overexpressed Apo A-I in MDA-MB-231 breast cancer cells was observed to have antitumor effects,inhibiting cell proliferation and migration.Subsequent studies on the mechanism of expression regulation revealed that estradiol(E2)/estrogen receptorα(ERα)signaling activates Apo A-I gene transcription in breast cancer cells.Mechanistically,our Ch IP-seq data showed that ERαdirectly binds to the estrogen response element(ERE)site within the Apo A-I gene and establishes an acetylation of histone 3 lysine 27(H3 K27 ac)-enriched chromatin microenvironment.Conversely,Fulvestrant(ICI 182780)treatment blocked ERαbinding to ERE within the Apo A-I gene and downregulated the H3 K27 ac level on the Apo A-I gene.Treatment with p300 inhibitor also significantly decreased the Apo A-I messenger RNA(m RNA)level in MCF7 cells.Furthermore,the analysis of data from The Cancer Genome Atlas(TCGA)revealed a positive correlation between ERαand Apo A-I expression in breast cancer tissues.Taken together,our study not only revealed the antitumor potential of Apo A-I at the cellular level,but also found that ERαpromotes the transcription of Apo A-I gene through direct genomic effects,and p300 may act as a co-activator of ERαin this process.

关 键 词：Apolipoprotein A-I(ApoA-I) Estrogen receptorα(ERα) Acetylation of histone 3 lysine 27(H3K27ac) p300 Breast cancer 

分 类 号：R737.9[医药卫生—肿瘤]