Oncotarget

Research Papers:

Identification of DBCCR1 as a suppressor in the development of lung cancer that is associated with increased DNA methyltransferase 1

Guoren Zhou, Jinjun Ye, Ying Fang, Zhi Zhang, Jingyuan Zhang, Lei Sun and Jifeng Feng _

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Oncotarget. 2017; 8:32821-32832. https://doi.org/10.18632/oncotarget.15826

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Abstract

Guoren Zhou1,*, Jinjun Ye2,*, Ying Fang1, Zhi Zhang3, Jingyuan Zhang4, Lei Sun5 and Jifeng Feng1

1Department of Chemotherapy, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210000, Jiangsu, China

2Department of Radiotherapy, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210000, Jiangsu, China

3Department of Thoracic Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210000, Jiangsu, China

4Department of Pathology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210000, Jiangsu, China

5Department of Medical Iconography, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210000, Jiangsu, China

*These authors have contributed equally to this work

Correspondence to:

Jifeng Feng, email: jsfjf2016@163.com

Keywords: lung cancer, DNA methyltransferase, tumor suppressor, DBCCR1, epigenetics

Received: January 04, 2017    Accepted: February 08, 2017    Published: March 02, 2017

ABSTRACT

Accumulating evidence has pointed to a role of the CpG island hypermethylation in the regulation of cancer-related genes in tumor progression. However, the biological impacts in cancer pathogenesis associated with down-regulation of such gene targets remains elusive. Here we focused on a potential target of hypermethylation, DBCCR1 (deleted in bladder cancer chromosome region 1), a gene encoding a candidate tumor suppressor. We found that the expression of DBCCR1 is significantly lower in the lung cancer tissues compared with adjacent non-tumor tissues of patients. Importantly, the decreased DBCCR1 was found correlated with more advanced stages of cancer, and with a significantly shorter survival of patients. Genetic silencing DBCCR1 in human lung cancer cell line A549 resulted in an enhanced proliferation, migration, and invasion capacity. Conversely, restoring DBCCR1 expression blocked the growth and inhibited the ability of cancer cell in migration and invasion. Interestingly, DBCCR1 attenuates the expression of DNMT1 (DNA methyltransferase 1), suggesting a reciprocal regulation between genetic silencing of cancer suppressor genes and activating DNA methylation. Our data thus implicates DBCCR1 downregulation as a potential module in the pathogenesis of lung cancer through DNA methylation.


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