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Specific activation of microRNA-127
with downregulation of the proto-oncogene BCL6 by
chromatin-modifying drugs in human cancer cells
Yoshimasa Saito1, Gangning
Liang1, 3, Gerda Egger1, 3, Jeffrey
M. Friedman1, Jody C. Chuang1, Gerhard
A. Coetzee2 and Peter A. Jones1,*
1Department
of Urology, Biochemistry, and Molecular Biology, Norris Comprehensive
Cancer Center, University of Southern California, Los Angeles,
California 90089. 2Urology and Preventive Medicine, Norris
Comprehensive Cancer Center, University of Southern California, Los
Angeles, California 90089.
Received 3 November 2005; revised 2 February 2006;
accepted 28 April 2006. Published: June 12, 2006. 3 These
authors contributed equally to this work.
*Corresponding Author, Ph: 323 865 0816; Fax: 323 865 0102
Received 3 November 2005; revised 2 February 2006;
accepted 28 April 2006. Published: June 12, 2006.
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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.
Author Keywords. DNA;
RNA; CELLCYCLE
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