Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells

• Published in: Cancer cell Vol. 9; no. 6; pp. 435 - 443
• Main Authors: Saito, Yoshimasa, Liang, Gangning, Egger, Gerda, Friedman, Jeffrey M., Chuang, Jody C., Coetzee, Gerhard A., Jones, Peter A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2006
• Subjects: Azacitidine - analogs & derivatives; Azacitidine - pharmacology; Cell Line, Tumor; CELLCYCLE; Chromatin - metabolism; CpG Islands; DNA; DNA Methylation - drug effects; DNA-Binding Proteins - metabolism; Down-Regulation; Epigenesis, Genetic; Histone Deacetylase Inhibitors; Humans; MicroRNAs - biosynthesis; MicroRNAs - metabolism; Phenylbutyrates - pharmacology; Promoter Regions, Genetic; Proto-Oncogene Proteins c-bcl-6 - metabolism; RNA; RNA; CELLCYCLE; DNA
• ISSN: 1535-6108; 1878-3686
• DOI: 10.1016/j.ccr.2006.04.020

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.