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

被引:1129
作者
Saito, Yoshimasa [1 ]
Liang, Gangning [1 ]
Egger, Gerda [1 ]
Friedman, Jeffrey M. [1 ]
Chuang, Jody C. [1 ]
Coetzee, Gerhard A. [1 ]
Jones, Peter A. [1 ]
机构
[1] Univ So Calif, Norris Comprehens Canc Ctr, Dept Urol Biochem & Mol Biol, Los Angeles, CA 90089 USA
关键词
D O I
10.1016/j.ccr.2006.04.020
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:435 / 443
页数:9
相关论文
共 29 条
[1]   Clustering and conservation patterns of human microRNAs [J].
Altuvia, Y ;
Landgraf, P ;
Lithwick, G ;
Elefant, N ;
Pfeffer, S ;
Aravin, A ;
Brownstein, MJ ;
Tuschl, T ;
Margalit, H .
NUCLEIC ACIDS RESEARCH, 2005, 33 (08) :2697-2706
[2]   The functions of animal microRNAs [J].
Ambros, V .
NATURE, 2004, 431 (7006) :350-355
[3]   Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs [J].
Cai, XZ ;
Hagedorn, CH ;
Cullen, BR .
RNA, 2004, 10 (12) :1957-1966
[4]   Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia [J].
Calin, GA ;
Dumitru, CD ;
Shimizu, M ;
Bichi, R ;
Zupo, S ;
Noch, E ;
Aldler, H ;
Rattan, S ;
Keating, M ;
Rai, K ;
Rassenti, L ;
Kipps, T ;
Negrini, M ;
Bullrich, F ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (24) :15524-15529
[5]   Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer [J].
Cameron, EE ;
Bachman, KE ;
Myöhänen, S ;
Herman, JG ;
Baylin, SB .
NATURE GENETICS, 1999, 21 (01) :103-107
[6]   Real-time quantification of microRNAs by stem-loop RT-PCR [J].
Chen, CF ;
Ridzon, DA ;
Broomer, AJ ;
Zhou, ZH ;
Lee, DH ;
Nguyen, JT ;
Barbisin, M ;
Xu, NL ;
Mahuvakar, VR ;
Andersen, MR ;
Lao, KQ ;
Livak, KJ ;
Guegler, KJ .
NUCLEIC ACIDS RESEARCH, 2005, 33 (20) :e179.1-e179.9
[7]   miR-15 and miR-16 induce apoptosis by targeting BCL2 [J].
Cimmino, A ;
Calin, GA ;
Fabbri, M ;
Iorio, MV ;
Ferracin, M ;
Shimizu, M ;
Wojcik, SE ;
Aqeilan, RI ;
Zupo, S ;
Dono, M ;
Rassenti, L ;
Alder, H ;
Volinia, S ;
Liu, CG ;
Kipps, TJ ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (39) :13944-13949
[8]   Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2′-deoxycytidine (decitabine) treatment [J].
Daskalakis, M ;
Nguyen, TT ;
Nguyen, C ;
Guldberg, P ;
Köhler, G ;
Wijermans, P ;
Jones, PA ;
Lübbert, M .
BLOOD, 2002, 100 (08) :2957-2964
[9]   RNAi-mediated allelic trans-interaction at the imprinted Rtl1/Peg11 locus [J].
Davis, E ;
Caiment, F ;
Tordoir, X ;
Cavaillé, J ;
Ferguson-Smith, A ;
Cockett, N ;
Georges, M ;
Charlier, C .
CURRENT BIOLOGY, 2005, 15 (08) :743-749
[10]   Epigenetics in human disease and prospects for epigenetic therapy [J].
Egger, G ;
Liang, GN ;
Aparicio, A ;
Jones, PA .
NATURE, 2004, 429 (6990) :457-463