Oncogenic zinc finger protein ZNF322A promotes stem cell-like properties in lung cancer through transcriptional suppression of c-Myc expression
| العنوان: | Oncogenic zinc finger protein ZNF322A promotes stem cell-like properties in lung cancer through transcriptional suppression of c-Myc expression |
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| المؤلفون: | Li Ting Wu, Yu Ting Chen, Wu Wei Lai, Yang Chih Shieh, Yi Ching Wang, Jayu Jen, Chun Yen Liu |
| المصدر: | Cell Death and Differentiation |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Lung Neoplasms, Transcription, Genetic, Biology, medicine.disease_cause, Article, Proto-Oncogene Proteins c-myc, Transcriptome, Prognostic markers, 03 medical and health sciences, 0302 clinical medicine, Cancer stem cell, Tumor Cells, Cultured, medicine, Humans, Phosphorylation, Lung cancer, Molecular Biology, Transcription factor, Oncogene Proteins, Zinc finger, Cancer stem cells, Oncogenes, Cell Biology, medicine.disease, Cancer metabolism, Chromatin, 030104 developmental biology, A549 Cells, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Cancer research, Stem cell, Carcinogenesis, Transcription Factors |
| الوصف: | ZNF322A, a C2H2 zinc finger transcription factor, is an oncoprotein in lung cancer. However, the transcription mechanisms of ZNF322A in lung cancer stem cell-like reprogramming remain elusive. By integrating our chromatin immunoprecipitation-sequencing and RNA-sequencing datasets, we identified and validated the transcriptional targets of ZNF322A, which were significantly enriched in tumorigenic functions and developmental processes. Indeed, overexpression of ZNF322A promoted self-renewal ability and increased stemness-related gene expressions in vitro and in vivo. Importantly, ZNF322A bound directly to c-Myc promoter and recruited histone deacetylase 3 to transcriptionally suppress c-Myc expression, which in turn increased mitochondrial oxidative phosphorylation and promoted cell motility, thus maintaining stem cell-like properties of lung cancer. Clinically, ZNF322AHigh/c-MycLow expression profile was revealed as an independent indicator of poor prognosis in lung cancer patients. Our study provides the first evidence that ZNF322A-centered transcriptome promotes lung tumorigenesis and ZNF322A acts as a transcription suppressor of c-Myc to maintain lung cancer stem cell-like properties by shifting metabolism towards oxidative phosphorylation. |
| تدمد: | 1476-5403 1350-9047 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99637d74e145a89a05398052bbbf35a9Test https://doi.org/10.1038/s41418-018-0204-6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....99637d74e145a89a05398052bbbf35a9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765403 13509047 |
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