Epigenetic repression of long non-coding RNA MEG3 mediated by DNMT1 represses the p53 pathway in gliomas

Li,Jia; Bian,Er-Bao; He,Xiao-Jun; Ma,Chun-Chun; Zong,Gang; Wang,Hong-Liang; Zhao,Bing

doi:10.3892/ijo.2015.3285

Epigenetic repression of long non-coding RNA MEG3 mediated by DNMT1 represses the p53 pathway in gliomas

Authors:
- Jia Li
- Er-Bao Bian
- Xiao-Jun He
- Chun-Chun Ma
- Gang Zong
- Hong-Liang Wang
- Bing Zhao
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Affiliations: Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China
Published online on: December 10, 2015 https://doi.org/10.3892/ijo.2015.3285
Pages: 723-733

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Abstract

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.

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