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PMID: 16766263 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Cancer cell ·Vol. 9 ·No. 6 ·2006-06-00 ·Pages 435-43

Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA, Jones PA

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.

MeSH Terms
Azacitidine/analogs & derivatives,pharmacology Cell Line, Tumor Chromatin/metabolism CpG Islands DNA Methylation/drug effects DNA-Binding Proteins/metabolism Decitabine Down-Regulation Epigenesis, Genetic Histone Deacetylase Inhibitors Humans MicroRNAs/biosynthesis,metabolism Phenylbutyrates/pharmacology Promoter Regions, Genetic Proto-Oncogene Mas Proto-Oncogene Proteins c-bcl-6/metabolism
Chemicals
BCL6 protein, human Chromatin DNA-Binding Proteins Histone Deacetylase Inhibitors MAS1 protein, human MicroRNAs Phenylbutyrates Proto-Oncogene Mas Proto-Oncogene Proteins c-bcl-6 Decitabine 4-phenylbutyric acid Azacitidine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Saito Yoshimasa
Department of Urology, Biochemistry, and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089, USA.
Liang Gangning
Egger Gerda
Friedman Jeffrey M
Chuang Jody C
Coetzee Gerhard A
Jones Peter A
Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1535-6108
Published
2006-06-00
Pages
435-43
Language
English
Region
United States
NLM ID
101130617
Subset
IM
Grants
NCI NIH HHS · P30 CA 014089 · United States
NCI NIH HHS · R01 CA 82422 · United States
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