Document Detail


Involvement of the miR17 pathway in glucocorticoid -induced cell death in pediatric acute lymphoblastic leukemia.
MedLine Citation:
PMID:  22475310     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Abstract Analysis of the microRNA transcriptome following dexamethasone treatment of the acute lymphocytic leukemia (ALL) cell line RS4;11 showed a global down-regulation of microRNA levels. MIR17HG was rapidly down-regulated following treatment, with ChIP analysis demonstrating the promoter to be a direct target of GC-transcriptional repression and revealing the miR17-92 cluster as a prime target for dexamethasone-induced repression. The loss of miR17 family expression and concomitant increases in the miR17 target Bim occurred in an additional ALL cell line SUP-B15 but not in the dexamethasone-resistant REH Alteration of miR17 levels through upregulation or inhibition resulted in the decrease and increase, respectively, in Bim protein levels and dexamethasone-induced cell death. Primary ex vivo ALL cells that underwent apoptosis induced by dexamethasone also down-regulated miR17 levels. Thus, down-regulation of miR17 plays an important role in glucocorticoid-induced cell death suggesting that targeting miR17 may improve the current ALL combination therapy.
Authors:
Masako Harada; Katja Pokrovskaja Tamm; Stefan Söderhäll; Mats Heyman; Dan Grander; Martin Corcoran
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-4
Journal Detail:
Title:  Leukemia & lymphoma     Volume:  -     ISSN:  1029-2403     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007422     Medline TA:  Leuk Lymphoma     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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