Involvement of miR17 pathway in glucocorticoid-induced cell death in pediatric acute lymphoblastic leukemia
M Harada, K Pokrovskaja-Tamm, S Söderhäll… - Leukemia & …, 2012 - Taylor & Francis
M Harada, K Pokrovskaja-Tamm, S Söderhäll, M Heyman, D Grander, M Corcoran
Leukemia & lymphoma, 2012•Taylor & FrancisAbstract Analysis of the microRNA transcriptome following dexa-methasone 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 …
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 …
Abstract
Analysis of the microRNA transcriptome following dexa- methasone 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.
![](/scholar/images/qa_favicons/tandfonline.com.png)
以上显示的是最相近的搜索结果。 查看全部搜索结果