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Molecular Cancer
Published in: Molecular Cancer 1/2011

Open Access 01-12-2011 | Research

MiR-185 Targets the DNA Methyltransferases 1 and Regulates Global DNA Methylation in human glioma

Authors: Zuping Zhang, Hailin Tang, Zeyou Wang, Baoxin Zhang, Wei Liu, Hongmei Lu, Lan Xiao, Xiaoping Liu, Rong Wang, Xiaoling Li, Minghua Wu, Guiyuan Li

Published in: Molecular Cancer | Issue 1/2011

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Abstract

Background

Perturbation of DNA methylation is frequent in cancers and has emerged as an important mechanism involved in tumorigenesis. To determine how DNA methylation is modified in the genome of primary glioma, we used Methyl-DNA immunoprecipitation (MeDIP) and Nimblegen CpG promoter microarrays to identify differentially DNA methylation sequences between primary glioma and normal brain tissue samples.

Methods

MeDIP-chip technology was used to investigate the whole-genome differential methylation patterns in glioma and normal brain tissues. Subsequently, the promoter methylation status of eight candidate genes was validated in 40 glioma samples and 4 cell lines by Sequenom's MassARRAY system. Then, the epigenetically regulated expression of these genes and the potential mechanisms were examined by chromatin immunoprecipitation and quantitative real-time PCR.

Results

A total of 524 hypermethylated and 104 hypomethylated regions were identified in glioma. Among them, 216 hypermethylated and 60 hypomethylated regions were mapped to the promoters of known genes related to a variety of important cellular processes. Eight promoter-hypermethylated genes (ANKDD1A, GAD1, HIST1H3E, PCDHA8, PCDHA13, PHOX2B, SIX3, and SST) were confirmed in primary glioma and cell lines. Aberrant promoter methylation and changed histone modifications were associated with their reduced expression in glioma. In addition, we found loss of heterozygosity (LOH) at the miR-185 locus located in the 22q11.2 in glioma and induction of miR-185 over-expression reduced global DNA methylation and induced the expression of the promoter-hypermethylated genes in glioma cells by directly targeting the DNA methyltransferases 1.

Conclusion

These comprehensive data may provide new insights into the epigenetic pathogenesis of human gliomas.
Appendix
Available only for authorised users
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Metadata
Title
MiR-185 Targets the DNA Methyltransferases 1 and Regulates Global DNA Methylation in human glioma
Authors
Zuping Zhang
Hailin Tang
Zeyou Wang
Baoxin Zhang
Wei Liu
Hongmei Lu
Lan Xiao
Xiaoping Liu
Rong Wang
Xiaoling Li
Minghua Wu
Guiyuan Li
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2011
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-10-124

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