title: MiR-185 targets the DNA methyltransferases 1 and regulates global DNA methylation in human glioma.
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.
  
  
  CONCLUSIONS
  These comprehensive data may provide new insights into the epigenetic pathogenesis of human gliomas.
authors.affiliation: Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education Central South University, Hunan, PR China.
authors.forename: Zuping
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hailin
authors.initials: H
authors.lastname: Tang
authors.forename: Zeyou
authors.initials: Z
authors.lastname: Wang
authors.forename: Baoxin
authors.initials: B
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Hongmei
authors.initials: H
authors.lastname: Lu
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Minghua
authors.initials: M
authors.lastname: Wu
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D052138:Genes, Neoplasm; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018895:Microsatellite Repeats; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D017422:Sequence Analysis, DNA
chemical_list: C552431:MIRN185 microRNA, human; D035683:MicroRNAs; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases