Oncotarget

Research Papers:

The rs1550117 A>G variant in DNMT3A gene promoter significantly increases non-small cell lung cancer susceptibility in a Han Chinese population

Jingdong Wang, Chade Li, Fengting Wan, Zhou Li, Jingli Zhang, Jiankun Zhang, Xianhong Feng, Liang Tang and Bifeng Chen _

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Oncotarget. 2017; 8:23470-23478. https://doi.org/10.18632/oncotarget.15625

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Abstract

Jingdong Wang1,*, Chade Li1,*, Fengting Wan1, Zhou Li1, Jingli Zhang1, Jiankun Zhang1, Xianhong Feng2, Liang Tang3, Bifeng Chen1

1Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, China

2Clinical Laboratory, Wuhan Xinzhou District People's Hospital, Wuhan, China

3Department of Human Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha, China

*These authors contributed equally to this work

Correspondence to:

Bifeng Chen, email: cbifeng@whut.edu.cn

Liang Tang, email: tlcool318@163.com

Keywords: non-small cell lung cancer, DNMT3A, rs1550117, Han Chinese population

Received: September 20, 2016     Accepted: February 14, 2017     Published: February 22, 2017

ABSTRACT

In this study, we conducted a case-control study to explore the association between rs1550117 A>G variant of DNMT3A gene promoter and non-small cell lung cancer (NSCLC) susceptibility in a Han Chinese population. The genotyping of rs1550117 A>G variant was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Allele G of rs1550117 was associated with an increased risk of NSCLC. Moreover, individuals carrying the GG genotypes had a higher risk to develop NSCLC than the AA and GA genotype carriers. Further stratified analysis showed that rs1550117 A>G was significantly related to age (> 60 years), male, smoking and drinking. In vivo detection of DNMT3A mRNA levels in NSCLC tissues and in vitro luciferase assays consistently showed that the allele G significantly decreased DNMT3A transcription. Additional functional analysis revealed that the increased binding affinity of transcription repressor SP1, which was associated with allele G of rs1550117, led to the significant decreased expression of DNMT3A. Collectively, our results propose a suppression role of DNMT3A in NSCLC development and emphasize the dual roles of DNMT3A in tumorigenesis.


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