Cancer-related transcriptional targets of the circadian gene NPAS2 identified by genome-wide ChIP-on-chip analysis.
Cancer-related transcriptional targets of the circadian gene NPAS2 identified by genome-wide ChIP-on-chip analysis.
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DOI：
10.1016/j.canlet.2009.04.017
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发表时间：
2009-11-01
期刊：
影响因子：
9.7
通讯作者：
Zhu, Yong
中科院分区：
文献类型：
--
作者：
Yi, Chun-Hui;Zheng, Tongzhang;Leaderer, Derek;Hoffman, Aaron;Zhu, Yong
转录因子NPAS 2是9个人类核心昼夜节律基因之一，通过调节24小时昼夜节律影响各种生物过程。最近，已经表明NPAS 2是人类癌症中的风险生物标志物，并且通过影响癌症相关基因表达和相关生物学途径在肿瘤发生中发挥作用。然而，很难研究NPAS 2在癌症发展中的生物学参与，因为对其直接转录靶点知之甚少。本研究的目的是建立一个转录谱的基因调控的NPAS 2，使用人结合ChIP芯片分析的NPAS 2在MCF-7细胞。这种全基因组定位方法鉴定了26个含有潜在NPAS 2结合区域的基因。随后的实时PCR检测证实了这些靶点中的16个，其中9个基因（ARHGAP 29、CDC 25 A、CDKN 2AIP、CX 3CL 1、ELF 4、GNAL、KDELR 1、POU 4F 2和THRA）在肿瘤发生中具有已知的作用。此外，对这些经验证的NPAS 2靶点的网络分析显示，所有9个基因与REN一起参与了“癌症，细胞周期，神经疾病”网络。这些结果报告了NPAS 2的直接转录靶点的第一个列表，并将阐明昼夜节律基因在肿瘤发生中的作用。
The transcription factor NPAS2 is one of nine human core circadian genes that influence a variety of biological processes by regulating the 24-h circadian rhythm. Recently, it has been shown that NPAS2 is a risk biomarker in human cancers and plays a role in tumorigenesis by affecting cancer-related gene expression, and relevant biological pathways. However, it is difficult to study the biological involvement of NPAS2 in cancer development, as little is known about its direct transcriptional targets. The aim of the current study is to create a transcriptional profile of genes regulated by NPAS2, using a human binding ChIP-on-chip analysis of NPAS2 in MCF-7 cells. This genome-wide mapping approach identified 26 genes that contain potential NPAS2 binding regions. Subsequent real-time PCR assays confirmed 16 of these targets, and 9 of these genes (ARHGAP29, CDC25A, CDKN2AIP, CX3CL1, ELF4, GNAL, KDELR1, POU4F2, and THRA) have a known role in tumorigenesis. In addition, a networking analysis of these validated NPAS2 targets revealed that all nine genes, together with REN, are involved in a “Cancer, Cell cycle, Neurological Disease” network. These results report the first list of direct transcriptional targets of NPAS2 and will shed light on the role of circadian genes in tumorigenesis.
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