Multi-omics approaches identify SF3B3 and SIRT3 as candidate autophagic regulators and druggable targets in invasive breast carcinoma
| العنوان: | Multi-omics approaches identify SF3B3 and SIRT3 as candidate autophagic regulators and druggable targets in invasive breast carcinoma |
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| المؤلفون: | Yang An, Jin Zhang, Xiaoxi Zeng, Yuqian Zhao, Shouyue Zhang, Ziyi Qin, Heng Xu, Bo Liu |
| المصدر: | Acta Pharmaceutica Sinica. B Acta Pharmaceutica Sinica B, Vol 11, Iss 5, Pp 1227-1245 (2021) |
| بيانات النشر: | Elsevier BV, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Druggable target, Programmed cell death, Candidate gene, CNA, copy number alteration, Regulator, Druggability, RM1-950, Biology, Autophagic regulator, TNBC, triple-negative breast cancer, SIRT3, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, BRCA, invasive breast carcinoma, ATG, autophagy-related gene, GO, Gene Ontology, Gene expression, medicine, General Pharmacology, Toxicology and Pharmaceutics, Migration, SNF, similarity network fusion, 030304 developmental biology, 0303 health sciences, LASSO, least absolute shrinkage and selection operator, Autophagy, SF3B3, medicine.disease, Multi-omics approach, PFS, progression-free survival, Invasive breast carcinoma, MET, DNA methylation, Anti-proliferation, EXP, gene expression, 030220 oncology & carcinogenesis, DNA methylation, Cancer research, TCGA, The Cancer Genome Atlas, Original Article, Therapeutics. Pharmacology |
| الوصف: | 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. Graphical abstract This study provides multi-omics approaches to identify some key candidate autophagic regulators, such as the negative regulator SF3B3 and positive regulator SIRT3 in invasive breast carcinoma, and highlight them as new druggable targets.Image 1 |
| تدمد: | 2211-3835 |
| DOI: | 10.1016/j.apsb.2020.12.013 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e5006d7fc616dab06691f1dd1bec142 https://doi.org/10.1016/j.apsb.2020.12.013 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9e5006d7fc616dab06691f1dd1bec142 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22113835 |
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| DOI: | 10.1016/j.apsb.2020.12.013 |