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

2016; Impact Journals LLC; Volume: 7; Issue: 28 Linguagem: Inglês

10.18632/oncotarget.9866

1949-2553

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

RNA modifications and cancer

// Jian Bai 1 , Xue Zhang 2 , Kai Hu 3 , Bangqing Liu 1 , Haiyong Wang 3 , Angui Li 3 , Feng Lin 3 , Lifei Zhang 1 , Xiaolin Sun 3 , Zhenzong Du 1, 4 , Jianfei Song 1, 4 1 Department of Thoracic & Cardiovascular Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin, China 2 Department of ICU, The Second Affiliated Hospital of Guilin Medical University, Guilin, China 3 Department of Thoracic & Cardiovascular Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, China 4 Current 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.