Abstract
Abstract DNA methylation mediated by DNA methyltransferase 1 (DNMT1) plays an important role in carcinogenesis and self-renewal ability of cancer stem cells (CSCs). However, the function of DNMT1 in esophageal squamous cell carcinoma (ESCC) carcinogenesis, especially self-renewal ability of ESCC-CSCs remains unclear. In this study, we found a high expression of DNMT1 in both side population (SP) cells and sphere formation cells that represented as substitutes for CSCs in KYSE150 and EC109 ESCC cell lines. In addition, the expression of DNMT1 was decreased during the differentiation from SP to None-SP (NSP) in these ESCC cells. These results suggested that DNMT1 might have a role in regulating self-renewal and/or differentiation of ESCC-CSCs. To further investigate DNMT1 in ESCC carcinogenesis and self-renewal ability of ESCC-CSCs, we silenced the expression of DNMT1 in KYSE150 and EC109 ESCC cells using lentivirus-mediated RNA interference (RNAi). Our results showed that ablation of DNMT1 expression in KYSE150 and EC109 ESCC cells resulted in decreased their CSCs by SP analysis and sphere formation assay. Meanwhile, ablation of DNMT1 expression inhibited malignant phenotypes in KYSE150 and EC109 cells, including cell proliferation, colony formation, migration and drug resistance abilities. Treatment of 5-aza-2'-deoxycytidine (5-aza-dC), a DNMT inhibitor that led to the degradation of DNMT1 protein by proteasome, revealed that numbers of CSCs and the malignant phenotypes of KYSE150 and EC109 ESCC cells were refrained significantly, including a dramatic inhibition of self-renewal ability of these ESCC-CSCs. Thus, our results indicated that DNMT1 was involved in ESCC carcinogenesis, especially in the maintenance of ESCC-CSCs, suggesting that DNMT1 could be a potential target for ESCC, especially ESCC-CSCs, therapy. Citation Format: Ying Teng, Xiying Yu, Hui Yuan, Liping Guo, Wei Jiang, Shih-Hsin Lu. DNMT1 is involved in esophageal squamous cell carcinoma (ESCC) and self-renewal ability of ESCC-cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1901. doi:10.1158/1538-7445.AM2017-1901
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