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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-12-24
pubmed:abstractText
Aberrant expression of miRNAs is associated with particular cancers showing tissue- and clinical-feature-specificity patterns. Some miRNA genes harboring or being embedded in CpG islands undergo methylation mediated silencing. MBP, methyl CpG binding protein, suppresses transcription through binding to methylated CpG dinucleotides. Expression of miR-373 has been reported to be suppressed in malignant bile duct cell lines. Bioinformatic prediction reveals that the transcription start site (TSS) of miR-373 is implanted in a 402 bp canonical CpG island containing 26 CpG dinucleotides. In this study, we aim to determine the epigenetic regulation of miR-373 gene in hilar cholangiocarcinoma. Taqman microRNA assay shows that down-regulation of miR-373 is closely associated with poor cell differentiation, advanced clinical stage and shorter overall and disease-free survival in hilar cholangiocarcinomas. Methylation analysis shows that the promoter-associated CpG island is hypermethylated which is consistent with the inhibition of miR-373. Chromatin immunoprecipitation (ChIP) assay indicates that down-regulation of miR-373 results from the selective recruitment of MBD2 to methylated CpG islands. In contrast, MBD2 knock-down by use of a specific siRNA promoted the expression of miR-373. Reactivation of miR-373 by pharmacologic induction of 5-aza-CdR and trichostatin A (TSA) led to decreased enrichment of MBD2 at CpG island regions. Enhanced expression of exogenous MBD2 in stable QBC939 cells which stably express pGL4-m373-prom induces strengthened recruitment of MBD2. Our findings suggest that miR-373 is a methylation-mediated gene and the implication of MBD2 in methylation-mediated suppression of miR-373 plays an important role in tumourigenesis and development in hilar cholangiocarcinoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1791-2431
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
443-51
pubmed:meshHeading
pubmed-meshheading:21165562-Adult, pubmed-meshheading:21165562-Aged, pubmed-meshheading:21165562-Aged, 80 and over, pubmed-meshheading:21165562-Base Sequence, pubmed-meshheading:21165562-Bile Duct Neoplasms, pubmed-meshheading:21165562-Bile Ducts, Intrahepatic, pubmed-meshheading:21165562-Cells, Cultured, pubmed-meshheading:21165562-Cholangiocarcinoma, pubmed-meshheading:21165562-CpG Islands, pubmed-meshheading:21165562-DNA Methylation, pubmed-meshheading:21165562-DNA-Binding Proteins, pubmed-meshheading:21165562-Down-Regulation, pubmed-meshheading:21165562-Female, pubmed-meshheading:21165562-Gene Expression Regulation, Neoplastic, pubmed-meshheading:21165562-Gene Silencing, pubmed-meshheading:21165562-Humans, pubmed-meshheading:21165562-Male, pubmed-meshheading:21165562-MicroRNAs, pubmed-meshheading:21165562-Middle Aged, pubmed-meshheading:21165562-Molecular Sequence Data, pubmed-meshheading:21165562-Promoter Regions, Genetic, pubmed-meshheading:21165562-Survival Analysis
pubmed:year
2011
pubmed:articleTitle
Methyl-CpG binding protein MBD2 is implicated in methylation-mediated suppression of miR-373 in hilar cholangiocarcinoma.
pubmed:affiliation
Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095, Jiefang Road, Wuhan 430030, PR China. zigachen45@gmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't