https://scholars.lib.ntu.edu.tw/handle/123456789/473331
標題: | Aryl hydrocarbon receptor downregulates MYCN expression and promotes cell differentiation of neuroblastoma | 作者: | HSUEH-FEN JUAN WEN-MING HSU HSIN-YU LEE YUNG-MING JENG Wang B.-J. Lu Y.-L. Yu I.-S. Shih Y.-Y. Lee H. |
公開日期: | 2014 | 出版社: | Public Library of Science | 卷: | 9 | 期: | 2 | 起(迄)頁: | e88795 | 來源出版物: | PLoS ONE | 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. ? 2014 Wu et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84896132280&doi=10.1371%2fjournal.pone.0088795&partnerID=40&md5=30aa975e4e539d5e65211e8479cbbb68 https://scholars.lib.ntu.edu.tw/handle/123456789/473331 |
ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0088795 | SDG/關鍵字: | aromatic hydrocarbon receptor; short hairpin RNA; aromatic hydrocarbon receptor; luciferase; MYCN protein, human; nuclear protein; oligonucleotide; oncoprotein; primer DNA; article; cell differentiation; cell function; controlled study; correlational study; down regulation; gene amplification; gene control; gene dosage; gene expression; gene identification; genetic transcription; histopathology; human; human cell; human tissue; in vitro study; MYCN gene; neuroblastoma; oncogene; signal transduction; biology; cell differentiation; gene expression regulation; genetics; metabolism; neuroblastoma; nonparametric test; pathophysiology; physiology; real time polymerase chain reaction; reverse transcription polymerase chain reaction; RNA interference; tissue microarray; tumor cell line; Western blotting; Blotting, Western; Cell Differentiation; Cell Line, Tumor; Computational Biology; DNA Primers; Gene Expression Regulation, Neoplastic; Humans; Luciferases; Neuroblastoma; Nuclear Proteins; Oligonucleotides; Oncogene Proteins; Real-Time Polymerase Chain Reaction; Receptors, Aryl Hydrocarbon; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Statistics, Nonparametric; Tissue Array Analysis |
顯示於: | 病理學科所 |
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