Metagenomic characterization of lysine acetyltransferases in human cancer and their association with clinicopathologic features
| العنوان: | Metagenomic characterization of lysine acetyltransferases in human cancer and their association with clinicopathologic features |
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| المؤلفون: | Shomita Rode, Yuanyuan Jiang, Lanxin Liu, Rui Wang, Xuhui Guo, Zeng-Quan Yang, Hui Liu |
| المصدر: | Cancer Science |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, BRD4, copy number alteration, Lysine Acetyltransferases, Cell Survival, gene amplification, Gene Dosage, Gene Expression, Breast Neoplasms, Biology, Disease-Free Survival, Transcriptome, 03 medical and health sciences, breast cancer, 0302 clinical medicine, Breast cancer, Cell Line, Tumor, Neoplasms, Gene expression, Gene duplication, medicine, Humans, N-Terminal Acetyltransferase E, Epigenetics, Genetics, Genomics, and Proteomics, Gene, N-Terminal Acetyltransferase A, Cell Proliferation, Histone Acetyltransferases, TATA-Binding Protein Associated Factors, lysine acetyltransferase, Genome, Human, Original Articles, General Medicine, Prognosis, medicine.disease, CREB-Binding Protein, 030104 developmental biology, NAA10, Oncology, 030220 oncology & carcinogenesis, Mutation, Cancer research, Transcription Factor TFIID, Original Article, E1A-Associated p300 Protein, Transcription Factors |
| الوصف: | Lysine acetyltransferases (KATs) are a highly diverse group of epigenetic enzymes that play important roles in various cellular processes including transcription, signal transduction, and cellular metabolism. However, our knowledge of the genomic and transcriptomic alterations of KAT genes and their clinical significance in human cancer remains incomplete. We undertook a metagenomic analysis of 37 KATs in more than 10 000 cancer samples across 33 tumor types, focusing on breast cancer. We identified associations among recurrent genetic alteration, gene expression, clinicopathologic features, and patient survival. Loss‐of‐function analysis was carried out to examine which KAT has important roles in growth and viability of breast cancer cells. We identified that a subset of KAT genes, including NAA10, KAT6A, and CREBBP, have high frequencies of genomic amplification or mutation in a spectrum of human cancers. Importantly, we found that 3 KATs, NAA10, ACAT2, and BRD4, were highly expressed in the aggressive basal‐like subtype, and their expression was significantly associated with disease‐free survival. Furthermore, we showed that depletion of NAA10 inhibits basal‐like breast cancer growth in vitro. Our findings provide a strong foundation for further mechanistic research and for developing therapies that target NAA10 or other KATs in human cancer. Integrated genomic, transcriptomic, and clinicopathologic data and loss‐of‐function screens in a large cohort of primary tumors and cell lines identified a subset of lysine acetyltransferases (KATs), notably NAA10, that were significantly associated with cancer aggressiveness and poor prognosis. Loss‐of‐function analysis revealed that NAA10 had important roles in promoting cancer cell growth and survival. Our findings provide a strong foundation for further mechanistic research and for developing therapies that target NAA10 or other KATs in human cancer. |
| تدمد: | 1349-7006 1347-9032 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5dec2de7769ce9aa9c4ad7cd7ac4e658Test https://doi.org/10.1111/cas.14385Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5dec2de7769ce9aa9c4ad7cd7ac4e658 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13497006 13479032 |
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