Large-scale loss-of-function perturbations reveal a comprehensive epigenetic regulatory network in breast cancer  

作　　者：Yumei Wang Haiyan Wang Wei Shao Yuhui Chen Yu Gui Chao Hu Xiaohong Yi Lijun Huang Shasha Li Dong Wang 

机构地区：[1]School of Basic Medical Sciences,State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China [2]Department of Pathology,School of Medicine,Qinghai University,Xining 810001,China [3]Omics Biosciences Inc,Beijing 100871,China [4]Laboratory of Integrative Medicine,Clinical Research Center for Breast,State Key Laboratory of Biotherapy,West China Hospital,Sichuan University and Collaborative Innovation Center,Chengdu 610041,China [5]State Key Laboratory of Southwestern Chinese Medicine Resources,School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China [6]Department of Endocrinology and Metabolism,Guangdong Provincial Key Laboratory of Diabetology&Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity Research,Medical Center for Comprehensive Weight Control,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China

出　　处：《Cancer Biology & Medicine》2024年第1期83-103,共21页癌症生物学与医学（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(Grant No.82172723);the Natural Science Foundation of Sichuan(Grant Nos.2023NSFSC1828 and 2022NSFSC1289);the“Xinglin Scholar”Scientific Research Promotion Plan of Chengdu University of Transitional Chinese Medicine(Grant No.BSH2021003);the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.ZYYCXTD-D-202209);the Research Funding of Department of Science and Technology of Qinghai Province(Grant No.2023-ZJ-729)。

摘　　要：Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive.It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets.Methods:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators.Then,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer.Results:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific functions.We discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and CBX3.Moreover,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation.Notably,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer.Conclusions:Our work deciphered the extensive regulation among hundreds of epigenetic regulators.The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.

关 键 词：Epigenetic regulators breast cancer regulatory network HTS^(2) 

分 类 号：R737.9[医药卫生—肿瘤]