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

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Acta Pharmaceutica Sinica B 2021年第5期11卷 1227-1245页

作者： Shouyue Zhang Jin Zhang Yang An Xiaoxi Zeng Ziyi Qin Yuqian Zhao Heng Xu Bo Liu State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityChengdu 610041China Department of Laboratory Medicine State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Department of Plastic Surgery Peking University Third HospitalBeijing 100191China Division of Plastic Surgery Brigham and Women's HospitalHarvard Medical SchoolBostonMA 02115USA West China Biomedical Big Data Center West China HospitalSichuan UniversityChengdu 610041China School of Pharmaceutical Sciences Health Science CenterShenzhen UniversityShenzhen 518060China

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 ***,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 ***3 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 ***,a novel small-molecule activator of SIRT3,1-methylbenzylamino amiodarone,was discovered to induce autophagy in vitro and in ***,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.

关键词： Invasive breast carcinoma multi-omics approach SIRT3 SF3B3 Autophagic regulator Anti-proliferation Migration Druggable target

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