Department of Gastroenterology, Beijing Friendship Hospital-Capital Medical University, Yongan Road 95, Beijing, China.
Dis Esophagus. 2011 Nov;24(8):601-10. doi: 10.1111/j.1442-2050.2011.01199.x. Epub 2011 May 3.
To explore the role of DNA methyltransferase 1 (DNMT1) in esophageal squamous cell carcinoma (ESCC) and the potential of DNMT1-targeted small interfering RNA as ESCC therapy, we examined expression changes of DNMT1 in ESCC and investigated the effect of DNMT1 knockdown by RNA interference in a human ESCC cell line, KYSE30. DNMT1 messenger RNA was over-expressed in seven out of 12 ESCC samples, and the percentage of cells expressing DNMT1 was significantly higher in ESCC tissues compared with paired non-cancerous tissues. DNMT1 protein levels correlated with lymph node metastasis, but exhibited no correlation with sex, age, tumor site, or tumor differentiation. Knockdown of DNMT1 in KYSE30 cells using RNA interference resulted in a reduction of promoter methylation and re-expression of methyl-guanine methyl-transferase and retinoic acid receptors beta, inhibition of cell proliferation/viability and induction of cell apoptosis. These results indicate that DNMT1 over-expression is involved in ESCC and correlated with lymph node metastasis. Knockdown of DNMT1 led to promoter demethylation and re-expression of several tumor suppressor genes thereby inhibiting cell proliferation/viability and inducing cell apoptosis.
为了探索 DNA 甲基转移酶 1（DNMT1）在食管鳞状细胞癌（ESCC）中的作用，以及 DNMT1 靶向的小干扰 RNA 作为 ESCC 治疗的潜力，我们检测了 ESCC 中 DNMT1 的表达变化，并在人 ESCC 细胞系 KYSE30 中研究了 RNA 干扰敲低 DNMT1 的效果。在 12 个 ESCC 样本中，有 7 个样本中 DNMT1 的信使 RNA 过表达，与配对的非癌组织相比，ESCC 组织中表达 DNMT1 的细胞比例明显更高。DNMT1 蛋白水平与淋巴结转移相关，但与性别、年龄、肿瘤部位或肿瘤分化无关。使用 RNA 干扰在 KYSE30 细胞中敲低 DNMT1 导致启动子甲基化减少和甲基鸟嘌呤甲基转移酶和视黄酸受体β的重新表达，抑制细胞增殖/活力并诱导细胞凋亡。这些结果表明，DNMT1 过表达参与 ESCC 并与淋巴结转移相关。敲低 DNMT1 导致几个肿瘤抑制基因的启动子去甲基化和重新表达，从而抑制细胞增殖/活力并诱导细胞凋亡。
