Multi-omics approaches identify SF3B3 and SIRT3 as candidate autophagic regulators and druggable targets in invasive breast carcinoma

作     者：Shouyue Zhang Jin Zhang Yang An Xiaoxi Zeng Ziyi Qin Yuqian Zhao Heng Xu Bo Liu Shouyue Zhang;Jin Zhang;Yang An;Xiaoxi Zeng;Ziyi Qin;Yuqian Zhao;Heng Xu;Bo Liu

作者机构：State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China Department of Laboratory MedicineState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Department of Plastic SurgeryPeking University Third HospitalBeijing 100191China Division of Plastic SurgeryBrigham and Women's HospitalHarvard Medical SchoolBostonMA 02115USA West China Biomedical Big Data CenterWest China HospitalSichuan UniversityChengdu 610041China School of Pharmaceutical SciencesHealth Science CenterShenzhen UniversityShenzhen 518060China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第5期

页      面：1227-1245页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grants from National Science and Technology Major Project of the Ministry of Science and Technology of the People’s Republic of China(No.2018ZX09735005) National Natural Science Foundation of China(Grant Nos.81522028,81673452,81673455,81873939,81803365 and 81602953) Post-Doctor Research Project(2018M643510,China) Post-Doctor Research Project of West China Hospital,Sichuan University(Grant No.2018HXBH065,China) supported by the grant from“The Recruitment Program of Global Young Experts”(known as“the Thousand Young Talents Plan”,China)。 

主　　题：Invasive breast carcinoma Multi-omics approach SIRT3 SF3B3 Autophagic regulator Anti-proliferation Migration Druggable target 

摘      要：Autophagy is a critical cellular homeostatic mechanism,and its dysfunction is linked to invasive breast carcinoma(BRCA).Recently,several omics methods have been applied to explore autophagic regulators in BRCA;however,more reliable and robust approaches for identifying crucial regulators and druggable targets remain to be discovered.Thus,we report here the results of multi-omics approaches to identify potential autophagic regulators in BRCA,including gene expression(EXP),DNA methylation(MET)and copy number alterations(CNAs)from The Cancer Genome Atlas(TCGA).Newly identified candidate genes,such as SF3 B3,TRAPPC10,SIRT3,MTERFD1,and FBXO5,were confirmed to be involved in the positive or negative regulation of autophagy in BRCA.SF3 B3 was identified firstly as a negative autophagic regulator,and siRNA/shRNA-SF3 B3 were shown to induce autophagyassociated cell death in in vitro and in vivo breast cancer models.Moreover,a novel small-molecule activator of SIRT3,1-methylbenzylamino amiodarone,was discovered to induce autophagy in vitro and in vivo.Together,these results provide multi-omics approaches to identify some key candidate autophagic regulators,such as the negative regulator SF3 B3 and positive regulator SIRT3 in BRCA,and highlight SF3 B3 and SIRT3 as new druggable targets that could be used to fill the gap between autophagy and cancer drug development.