沉默DNA甲基转移酶1（DNMT1）通过抑制RASSF1A和DAPK的甲基化来抑制食管癌的增殖、转移和侵袭。

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

作者信息

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

机构信息

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

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

出版信息

Oncotarget. 2016 Jul 12;7(28):44129-44141. doi: 10.18632/oncotarget.9866.

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.

我们之前的研究表明，DNMT1在食管鳞状细胞癌（ESCC）中上调，这与肿瘤抑制因子的甲基化有关。在本研究中，我们探究了DNMT1在ESCC中的作用。我们发现，沉默DNMT1可抑制三种不同的ESCC细胞K150、K410和K450的增殖、转移和侵袭。我们还发现，沉默DNMT1可诱导K150、K410和K450细胞发生G1期阻滞和细胞凋亡。体内研究表明，沉默DNMT1可抑制裸鼠肿瘤生长。此外，沉默DNMT1可增加ESCC细胞和裸鼠ESCC异种移植瘤中肿瘤抑制基因RASSF1A和DAPK的表达。而且，沉默DNMT1可降低RASSF1A和DAPK启动子的甲基化水平。总之，我们的数据表明，沉默DNMT1通过抑制RASSF1A和DAPK的甲基化来抑制ESCC的增殖、转移和侵袭。