Journal
LEUKEMIA & LYMPHOMA
Volume 53, Issue 10, Pages 2041-2050Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/10428194.2012.678004
Keywords
Chemotherapeutic approaches; lymphoid leukemia; cell cycle and apoptosis; changes; drug resistance; molecular genetics; pharmacotherapeutics
Categories
Funding
- Radiumhemmets Cancer fonden
- Cancerfonden
- Barncancerfonden
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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 chromatin immunoprecipitation (ChIP) analysis demonstrating the promoter to be a direct target of glucocorticoid (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 up-regulation or inhibition resulted in an 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.
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