Oncotarget

Research Papers:

DNA methylation of METTL7A gene body regulates its transcriptional level in thyroid cancer

Shasha Zhou, Yihang Shen, Min Zheng, Linlin Wang, Raymond Che, Wanning Hu and Pin Li _

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Oncotarget. 2017; 8:34652-34660. https://doi.org/10.18632/oncotarget.16147

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Abstract

Shasha Zhou1,*, Yihang Shen2,*, Min Zheng3,*, Linlin Wang4,5, Raymond Che6, Wanning Hu3 and Pin Li1

1Department of Endocrinology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, 200040, People’s Republic of China

2Institute of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, 200032, People’s Republic of China

3Department of Oncology of Tangshan People’s Hospital & Tangshan Cancer Hospital, North China University of Science and Technology, Tangshan, Hebei, 063001, People’s Republic of China

4Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, 250013, People’s Republic of China

5Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, 250117, People’s Republic of China

6University of Hawaii Cancer Center, University of Hawaii, Honolulu, Hawaii, 96814, USA

*These authors have equally contributed to this work

Correspondence to:

Pin Li, email: lipinpub888@163.com

Keywords: DNA methylation, gene body, EZH2, METTL7A, thyroid cancer

Received: January 12, 2017    Accepted: February 08, 2017    Published: March 13, 2017

ABSTRACT

DNA methylation is the best-studied epigenetic mechanism for regulating gene transcription and maintaining genome stability. Current research progress of transcriptional regulation by DNA methylation mostly focuses on promoter region where hypomethylated CpG islands are present transcriptional activity, as hypermethylated CpG islands generally result in gene repression. Recently, the DNA methylation patterns across the gene body (intragenic methylation) have increasingly attracted attention towards their role in transcriptional regulation and efficiency, due to the improvement of numerous genome-wide DNA methylation profiling studies. However, the function and mechanism of gene body methylation is still unclear. In this study, we revealed that the methylation level of METTL7A, a seldom studied gene, was downregulated in thyroid cancer compared to normal thyroid cells in vivo and in vitro. Moreover, we determined the methylation level of one CpG site at the exon of the METTL7A gene body impacted the transcriptional activity. Through generating a mutation of this CpG site (CG to CC) of METTL7A exogenous vector artificially in vitro, we observed higher RNA polymerase II recruitment and a declined enrichment of methyl-CpG binding protein-2 in gene body of METTL7A, in papillary thryoid cancer cells (BCPAP) compared to normal thryoid cells. Finally, we revealed that EZH2, a subunit of polycomb repressor complex 2, dominant in thyroid cancer, might be responsible for regulating gene body methylation of METTL7A. Our study depicted the DNA methylation patterns and the transcriptional regulatory mechanism of the gene body in thyroid cancer. Furthermore, this study provides new insight into potential future avenues, for therapies targeting cancer.


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