4.7 Article

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

期刊

ACTA PHARMACEUTICA SINICA B
卷 11, 期 5, 页码 1227-1245

出版社

INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2020.12.013

关键词

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

资金

  1. National Science and Technology Major Project of the Ministry of Science and Technology of the People's Republic of China [2018ZX09735005]
  2. National Natural Science Foundation of China [81522028, 81673452, 81673455, 81873939, 81803365, 81602953]
  3. Post-Doctor Research Project, China [2018M643510]
  4. Post-Doctor Research Project of West China Hospital, Sichuan University, China [2018HXBH065]
  5. The Recruitment Program of Global Young Experts

向作者/读者索取更多资源

Multi-omics approaches were used to identify potential autophagic regulators in BRCA, revealing SF3B3 as a negative regulator and SIRT3 as a positive regulator. These findings highlight SF3B3 and SIRT3 as new druggable targets in bridging the gap between autophagy and cancer drug development.
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 SF3B3, TRAPPC10, SIRT3, MTERFD1, and FBXO5, were confirmed to be involved in the positive or negative regulation of autophagy in BRCA. SF3B3 was identified firstly as a negative autophagic regulator, and siRNA/shRNA-SF3B3 were shown to induce autophagy-associated 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 SF3B3 and positive regulator SIRT3 in BRCA, and highlight SF3B3 and SIRT3 as new druggable targets that could be used to fill the gap between autophagy and cancer drug development. (C) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

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