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

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.

• Authors: Jia Li, Er-Bao Bian, Xiao-Jun He, Chun-Chun Ma, Gang Zong, Hong-Liang Wang, Bing Zhao
• Journal: International journal of oncology (Int J Oncol) Vol. 48 Issue 2 Pg. 723-33 (Feb 2016) ISSN: 1791-2423 [Electronic] Greece
• PMID: 26676363 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MEG3 non-coding RNA, human
• RNA, Long Noncoding
• TP53 protein, human
• Tumor Suppressor Protein p53
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA (Cytosine-5-)-Methyltransferases
• DNMT1 protein, human

Topics

• Apoptosis (genetics)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA (Cytosine-5-)-Methyltransferases (genetics)
• DNA Methylation (genetics)
• Down-Regulation (genetics)
• Epigenesis, Genetic (genetics)
• Epigenetic Repression (genetics)
• Gene Expression Regulation, Neoplastic (genetics)
• Glioma (genetics)
• Humans
• Promoter Regions, Genetic (genetics)
• RNA, Long Noncoding (genetics)
• Tumor Suppressor Protein p53 (genetics)