Oncotarget

Research Papers:

Analysis of the transcriptional regulation of cancer-related genes by aberrant DNA methylation of the cis-regulation sites in the promoter region during hepatocyte carcinogenesis caused by arsenic

Zhuang Miao _, Lin Wu, Ming Lu, Xianzhi Meng, Bo Gao, Xin Qiao, Weihui Zhang and Dongbo Xue

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Oncotarget. 2015; 6:21493-21506. https://doi.org/10.18632/oncotarget.4085

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Abstract

Zhuang Miao1, Lin Wu1, Ming Lu2, Xianzhi Meng1, Bo Gao1, Xin Qiao2, Weihui Zhang1, Dongbo Xue1

1Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China

2Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

Correspondence to:

Dongbo Xue, e-mail: dongbo_xue@126.com

Keywords: carcinogenesis, DNA methylation, arsenic exposure

Received: March 21, 2015     Accepted: May 11, 2015     Published: May 25, 2015

ABSTRACT

Liver is the major organ for arsenic methylation metabolism and may be the potential target of arsenic-induced cancer. In this study, normal human liver cell was treated with arsenic trioxide, and detected using DNA methylation microarray. Some oncogenes, tumor suppressor genes, transcription factors (TF), and tumor-associated genes (TAG) that have aberrant DNA methylation have been identified. However, simple functional studies of genes adjacent to aberrant methylation sites cannot well reflect the regulatory relationship between DNA methylation and gene transcription during the pathogenesis of arsenic-induced liver cancer, whereas a further analysis of the cis-regulatory elements and their trans-acting factors adjacent to DNA methylation can more precisely reflect the relationship between them. MYC and MAX (MYC associated factor X) were found to participating cell cycle through a bioinformatics analysis. Additionally, it was found that the hypomethylation of cis-regulatory sites in the MYC promoter region and the hypermethylation of cis-regulatory sites in the MAX promoter region result in the up-regulation of MYC mRNA expression and the down-regulation of MAX mRNA, which increased the hepatocyte carcinogenesis tendency.


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PII: 4085