Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, 230601, China.
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, 230601, China.
Biomed Pharmacother. 2018 Oct;106:678-685. doi: 10.1016/j.biopha.2018.06.156. Epub 2018 Jul 11.
Malignant glioma is one of the most common primary human tumors in the central nervous system. The molecular mechanisms of the progression and development of glioma have been largely unexplored. In this study, we illustrated that the expression of Dok7 was downregulation in human glioma tissues. Dok7 overexpression significantly inhibits proliferation and colony formation in vitro, and the xenograft tumor formation in vivo. In addition, 5-Aza-2'-deoxycytidine (5-Aza), a DNA methylation inhibitor, preventing the loss of Dok7 expression by decreasing aberrant hypermethylation of Dok7 promoter in glioma cells. More importantly, DNMT1 knockdown induced the demethylation of Dok7 promoter, and enhanced the expression of Dok7 in gliomas. These results suggest that epigenetic silencing of Dok7 may provide a novel glioma treatment strategy.
恶性神经胶质瘤是中枢神经系统中最常见的原发性人类肿瘤之一。神经胶质瘤进展和发展的分子机制在很大程度上尚未被探索。在这项研究中，我们表明 Dok7 的表达在人神经胶质瘤组织中下调。Dok7 的过表达显著抑制体外增殖和集落形成，以及体内异种移植肿瘤形成。此外，DNA 甲基化抑制剂 5-氮杂-2'-脱氧胞苷（5-Aza）通过减少神经胶质瘤细胞中 Dok7 启动子的异常高甲基化来防止 Dok7 表达的丢失。更重要的是，DNMT1 敲低诱导 Dok7 启动子的去甲基化，并增强神经胶质瘤中 Dok7 的表达。这些结果表明，Dok7 的表观遗传沉默可能为神经胶质瘤的治疗提供一种新策略。
