Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells.
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.
Saito
Yoshimasa
Y
Department of Urology, Biochemistry, and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089, USA.
Liang
Gangning
G
Egger
Gerda
G
Friedman
Jeffrey M
JM
Chuang
Jody C
JC
Coetzee
Gerhard A
GA
Jones
Peter A
PA
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism*; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000077209:Decitabine; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D010654:Phenylbutyrates / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism*
C084103:BCL6 protein, human; D002843:Chromatin; D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; C000715470:MAS1 protein, human; D035683:MicroRNAs; D010654:Phenylbutyrates; D000090063:Proto-Oncogene Mas; D051560:Proto-Oncogene Proteins c-bcl-6; D000077209:Decitabine; C075773:4-phenylbutyric acid; D001374:Azacitidine