Epigenetic repression of long non-coding RNA MEG3 mediated by DNMT1 represses the p53 pathway in gliomas
Epigenetic repression of long non-coding RNA MEG3 mediated by DNMT1 represses the p53 pathway in gliomas
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DNMT1介导的长非编码RNA MEG3的表观遗传抑制抑制了胶质瘤中的p53通路
DOI：
10.3892/ijo.2015.3285
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发表时间：
2016-02-01
影响因子：
5.2
通讯作者：
Zhao, Bing
中科院分区：
文献类型：
--
作者：
Li, Jia;Bian, Er-Bao;Zhao, Bing
表观遗传调控在胶质瘤中起重要作用。然而，甲基化和长链非编码RNA （lncRNA）如何协同调节胶质瘤的进展在很大程度上是未知的。在这项研究中，我们发现在胶质瘤组织中，由于MEG3的高甲基化，MEG3的表达下调。用DNA甲基化抑制剂5-Aza-2'-脱氧胞苷（5-AzadC）治疗胶质瘤细胞可以减少MEG3启动子的异常超甲基化，防止MEG3表达的丧失。此外，DNMT1参与MEG3启动子甲基化，并与胶质瘤中MEG3的表达呈负相关。抑制DNMT1可抑制胶质瘤细胞的增殖、克隆形成并诱导细胞凋亡。重要的是，DNMT1的抑制促进了胶质瘤细胞中p53通路的激活。这些结果表明，dnmt1介导的MEG3高甲基化导致了胶质瘤中MEG3表达的缺失，随后抑制了p53通路。
Epigenetic regulation plays a significant role in gliomas. However, how methylation and long non-coding RNA (lncRNA) cooperates to regulate gliomas progression is largely unknown. In this investigation we showed that the downregulation of MEG3 expression due to hypermethylation of MEG3 was observed in gliomas tissues. Treatment of glioma cells with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine (5-AzadC) decreased aberrant hypermethylation of the MEG3 promoter and prevented the loss of MEG3 expression. In addition, DNMT1 was involved in MEG3 promoter methylation, and was inversely correlated with MEG3 expression in gliomas. The inhibition of DNMT1 repressed the proliferation, clone formation, and induced apoptosis in glioma cells. Importantly, the inhibition of DNMT1 contributed to the activation of p53 pathways in gliomas cells. These results suggest that DNMT1-mediated MEG3 hypermethylation caused the loss of MEG3 expression, followed by the inhibition of the p53 pathways in gliomas.