Oncotarget

Research Papers:

Silencing DNA methyltransferase 1 (DNMT1) inhibits proliferation, metastasis and invasion in ESCC by suppressing methylation of RASSF1A and DAPK

Jian Bai _, Xue Zhang, Kai Hu, Bangqing Liu, Haiyong Wang, Angui Li, Feng Lin, Lifei Zhang, Xiaolin Sun, Zhenzong Du and Jianfei Song

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Oncotarget. 2016; 7:44129-44141. https://doi.org/10.18632/oncotarget.9866

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Abstract

Jian Bai1, Xue Zhang2, Kai Hu3, Bangqing Liu1, Haiyong Wang3, Angui Li3, Feng Lin3, Lifei Zhang1, Xiaolin Sun3, Zhenzong Du1,4, Jianfei Song1,4

1Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, China

2Department of ICU, The Second Affiliated Hospital of Guilin Medical University, Guilin, China

3Department of Thoracic & Cardiovascular Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, China

4Current address: Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Lingui District, Guilin, China

Correspondence to:

Jianfei Song, email: guilinsjf@163.com

Zhenzong Du, email: duzhenzong@sina.com

Keywords: ESCC, DNA methyltransferase 1, methylation, RASSF1A, DAPK

Received: July 27, 2015     Accepted: March 31, 2016     Published: June 7, 2016

ABSTRACT

Our previous study showed DNMT1 is up-regulated in esophageal squamous cell carcinoma (ESCC), which is associated with methylation of tumor suppressors. In the current study, we investigate the role of DNMT1 in ESCC. We found silencing DNMT1 inhibited proliferation, metastasis and invasion of three different ESCC cells, K150, K410 and K450. We also found silencing DNMT1 induced G1 arrest and cell apoptosis in K150, K410 and K450 cells. In vivo study showed silencing DNMT1 suppressed tumor growth in nude mice. In addition, silencing DNMT1 increased expression of tumor suppressor genes, RASSF1A and DAPK, in ESCC cells and ESCC xenograft in nude mice. Moreover, silencing DNMT1 decreased methylation in promoter of RASSF1A and DAPK. In conclusion, our data demonstrated that silencing DNMT1 inhibits proliferation, metastasis and invasion in ESCC by suppressing methylation of RASSF1A and DAPK.


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