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| 題名: | Aryl hydrocarbon receptor downregulates MYCN expression and promotes cell differentiation of neuroblastoma |
| 作者: | 吳沛翊;Wu, Pei-Yi;Liao, Yung-Feng;Juan, Hsueh-Fen;Huang, Hsuan-Cheng;Wang, Bo-Jeng;Lu, Yen-Lin;Yu, I-Shing;Shih, Yu-Yin;Jeng, Yung-Ming;Hsu, Wen-Ming;Lee, Hsinyu |
| 貢獻者: | 生醫理工學院生命科學系 |
| 關鍵詞: | Amplification;Analysis;Apoptosis;Aromatic compounds;Biology;Blotting, Western;Cancer;Cell cycle;Cell differentiation;Cell Differentiation - physiology;Cell growth;Cell Line, Tumor;Computational Biology;Copy number;Differentiation (biology);Dioxin;Dioxins;DNA microarrays;DNA Primers - genetics;Ectopic expression;Gene expression;Gene Expression Regulation, Neoplastic - physiology;Gene regulation;Genes;Hospitals;Humans;Hydrocarbons;Life sciences;Luciferases;Medical prognosis;Medical research;Medicine;Mortality;MYCN gene;N-Myc Proto-Oncogene Protein;Neuroblastoma;Neuroblastoma - physiopathology;Nuclear Proteins - metabolism;Oligonucleotides;Oligonucleotides - genetics;Oncogene Proteins - metabolism;Prognosis;Real-Time Polymerase Chain Reaction;Receptors, Aryl Hydrocarbon - metabolism;Reverse Transcriptase Polymerase Chain Reaction;RNA Interference;Statistics, Nonparametric;Tissue Array Analysis;Tissues;Transcription;Tumorigenesis;Tumors |
| 日期: | 2014-02-21 |
| 上傳時間: | 2026-04-23 11:11:46 (UTC+8) |
| 出版者: | Public Library of Science;United States: Public Library of Science |
| 摘要: | 摘要： Neuroblastoma (NB) is the most common malignant disease of infancy. MYCN amplification is a prognostic factor for NB and is a sign of highly malignant disease and poor patient prognosis. In this study, we aimed to investigate novel MYCN-related genes and assess how they affect NB cell behavior. The different gene expression found in 10 MYCN amplification NB tumors and 10 tumors with normal MYCN copy number were analyzed using tissue oligonucleotide microarrays. Ingenuity Pathway Analysis was subsequently performed to identify the potential genes involved in MYCN regulation pathways. Aryl hydrocarbon receptor (AHR), a receptor for dioxin-like compounds, was found to be inversely correlated with MYCN expression in NB tissues. This correlation was confirmed in a further 14 human NB samples. Moreover, AHR expression in NB tumors was found to correlate highly with histological grade of differentiation. In vitro studies revealed that AHR overexpression in NB cells induced spontaneous cell differentiation. In addition, it was found that ectopic expression of AHR suppressed MYCN promoter activity resulting in downregulation of MYCN expression. The suppression effect of AHR on the transcription of MYCN was compensated for by E2F1 overexpression, indicating that E2F1 is involved in the AHR-regulating MYCN pathway. Furthermore, AHR shRNA promotes the expression of E2F1 and MYCN in NB cells. These findings suggest that AHR is one of the upstream regulators of MYCN. Through the modulation of E2F1, AHR regulates MYCN gene expression, which may in turn affect NB differentiation.
其他題名： PLoS One
出版者： United States: Public Library of Science
出版日期： 2014-02-21
出處： PloS one, 2014-02, Vol.9 (2), p.e88795
資源來源： Agricultural & Environmental Science Collection
版權： COPYRIGHT 2014 Public Library of Science
版權： 2014 Wu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
版權： 2014 Wu et al 2014 Wu et al
識別號： ISSN: 1932-6203
識別號： EISSN: 1932-6203
識別號： DOI: 10.1371/journal.pone.0088795
識別號： PMID: 24586395 |
| 顯示於類別: | [生命科學系] 期刊論文
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