Abstract
Expression profiling of T24 cells revealed that 17 out of 313 human miRNAs were upregulated more than 3-fold by simultaneous treatment with the chromatin-modifying drugs 5-aza-2'-deoxycytidine and 4-phenylbutyric acid. One of these, miR-127, is embedded in a CpG island and is highly induced from its own promoter after treatment. miR-127 is usually expressed as part of a miRNA cluster in normal cells but not in cancer cells, suggesting that it is subject to epigenetic silencing. In addition, the proto-oncogene BCL6, a potential target of miR-127, was translationally downregulated after treatment. These results suggest that DNA demethylation and histone deacetylase inhibition can activate expression of miRNAs that may act as tumor suppressors.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Azacitidine / analogs & derivatives
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Azacitidine / pharmacology
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Cell Line, Tumor
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Chromatin / metabolism*
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CpG Islands
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DNA Methylation / drug effects
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DNA-Binding Proteins / metabolism*
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Decitabine
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Down-Regulation
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Epigenesis, Genetic
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Histone Deacetylase Inhibitors
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Humans
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MicroRNAs / biosynthesis
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MicroRNAs / metabolism*
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Phenylbutyrates / pharmacology
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Promoter Regions, Genetic
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Proto-Oncogene Mas
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Proto-Oncogene Proteins c-bcl-6 / metabolism*
Substances
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BCL6 protein, human
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Chromatin
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DNA-Binding Proteins
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Histone Deacetylase Inhibitors
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MAS1 protein, human
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MicroRNAs
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Phenylbutyrates
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Proto-Oncogene Mas
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Proto-Oncogene Proteins c-bcl-6
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Decitabine
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4-phenylbutyric acid
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Azacitidine