Yang Shou-Mei, Li Su-Yi, Yu Hao-Bin, Li Jie-Ru, Sun Lei-Lei
Department of Medical Oncology, Anhui Provincial Cancer Hospital, Anhui Provincial Hospital,107 Huanhu Road East, Hefei, 230031, People's Republic of China.
Department of Medical Oncology, Anhui Provincial Cancer Hospital, Anhui Provincial Hospital,107 Huanhu Road East, Hefei, 230031, People's Republic of China.
Biomed Pharmacother. 2017 Jun;90:93-99. doi: 10.1016/j.biopha.2017.02.111. Epub 2017 Mar 24.
Increasing evidence shows that aberrant epigenetic regulation of tumor suppressor genes is a contributing factor to their altered expression in esophageal squamous cell carcinoma (ESCC). In the current study, we investigate the role of DOK7 in ESCC cells. We found that enforced expression of DOK7 inhibited the proliferation and invasion of ESCC cells. We also found that treatment of ESCC cells with the DNA methylation inhibitor, 5-aza-2-deoxycytidine (5-azadC), induced the demethylation of DOK7 in promoter and DOK7 expression. Moreover, silencing DNMT3A decreased methylation of DOK7 and increased DOK7 expression, followed by repressing the proliferation and invasion of ESCC cells. Collectively, our data indicated that silencing DNMT3A inhibits proliferation and invasion in ESCC cells by inducing demethylation of DOK7.
越来越多的证据表明，肿瘤抑制基因的异常表观遗传调控是其在食管鳞状细胞癌（ESCC）中表达改变的一个促成因素。在本研究中，我们调查了DOK7在ESCC细胞中的作用。我们发现，强制表达DOK7可抑制ESCC细胞的增殖和侵袭。我们还发现，用DNA甲基化抑制剂5-氮杂-2'-脱氧胞苷（5-azadC）处理ESCC细胞可诱导DOK7启动子去甲基化并增加DOK7表达。此外，沉默DNMT3A可降低DOK7的甲基化水平并增加DOK7表达，随后抑制ESCC细胞的增殖和侵袭。总体而言，我们的数据表明，沉默DNMT3A通过诱导DOK7去甲基化来抑制ESCC细胞的增殖和侵袭。
