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JMJD2A attenuation affects cell cycle and tumourigenic inflammatory gene regulation in lipopolysaccharide stimulated neuroectodermal stem cells

Title
JMJD2A attenuation affects cell cycle and tumourigenic inflammatory gene regulation in lipopolysaccharide stimulated neuroectodermal stem cells
Author
채영규
Keywords
Inflammation; JMJD2A; Cell cycle; Neuroectodermal stem cell; p53
Issue Date
2014-11
Publisher
ELSEVIER INC, 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
Citation
EXPERIMENTAL CELL RESEARCH, 권: 328, 호: 2, 페이지: 361-378
Abstract
JMJD2A is a lysine trimethyl-specific histone demethylase that is highly expressed in a variety of tumours. The role of JMJD2A in tumour progression remains unclear. The objectives of this study were to identify JMJD2A-regulated genes and understand the function of JMJD2A in p53- neuroectodermal stem cells (p53(-/-) NE-4Cs). We determined the effect of LPS as a model of inflammation in p53(-/-) NE-4Cs and investigated whether the epigenetic modifier JMJD2A alter the expression of tumourigenic inflammatory genes. Global gene expression was measured in JMJD2A knockdown (kd) p53(-/-) NE-4Cs and in LPS-stimulated JMJD2A-kd p5(3-/-) NE-4C cells. JMJD2A attenuation significantly down-regulated genes were Cdca2, Ccnd2, Ccnd1, Crebbp, IL6r alpha, and Stat3 related with cell cycle, proliferation, and inflammatory-disease responses. Importantly, some tumour-suppressor genes including Dapk3, Timp2 and TFPI were significantly up-regulated but were not affected by silencing of the JMJD2B. Furthermore, we confirmed the attenuation of JMJD2A also down-regulated Cdca2, Ccnd2, Crebbp, and Rest in primary NSCs isolated from the forebrains of E15 embryos of C57/BL6J mice with effective p53 inhibitor pifithrin-alpha (PFT-alpha). Transcription factor (TF) motif analysis revealed known binding patterns for CDC5, MYC, and CREB, as well as three novel motifs in JMJD2A-regulated genes. IPA established molecular networks. The molecular network signatures and functional gene-expression profiling data from this study warrants further investigation as an effective therapeutic target, and studies to elucidate the molecular mechanism of JMJD2A-kd-dependent effects in neuroectodermal stem cells should be performed. (C) 2014 Elsevier Inc. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S001448271400367X?via%3Dihubhttp://hdl.handle.net/20.500.11754/51366
ISSN
0014-4827; 1090-2422
DOI
10.1016/j.yexcr.2014.08.029
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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