Aryl hydrocarbon receptor downregulates MYCN expression and promotes cell differentiation of neuroblastoma

Pei Yi Wu, Yung Feng Liao, Hsueh Fen Juan, Hsuan Cheng Huang, Bo Jeng Wang, Yen-Lin Liu, I. Shing Yu, Yu Yin Shih, Yung Ming Jeng, Wen Ming Hsu, Hsinyu Lee

研究成果: 雜誌貢獻文章

20 引文 斯高帕斯(Scopus)

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.
原文英語
文章編號e88795
期刊PLoS One
9
發行號2
DOIs
出版狀態已發佈 - 二月 21 2014
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

引用此

Wu, P. Y., Liao, Y. F., Juan, H. F., Huang, H. C., Wang, B. J., Liu, Y-L., Yu, I. S., Shih, Y. Y., Jeng, Y. M., Hsu, W. M., & Lee, H. (2014). Aryl hydrocarbon receptor downregulates MYCN expression and promotes cell differentiation of neuroblastoma. PLoS One, 9(2), [e88795]. https://doi.org/10.1371/journal.pone.0088795