Sp1/NFkB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia (Cancer Cell, 2010, 17:333-347)

報告日期: 2010/10/22
報告時間: 15:10/16:00
報告學生: 洪家揚
講評老師: 呂增宏
附件下載:

Full text: http://basicmed.med.ncku.edu.tw/admin/up_img/991022-1.pdf

Sp1/NFkB/HDAC/miR-29b regulatory network in KIT-Driven myeloid leukemia

Cancer Cell 17, 333–347, April 13, 2010

 

Speaker: Chia-Yang Hung

Commentator: Tzeng-Horng Leu

Date: 2010.10.22  15:10~16:00

 

Abstract:

    The biologic and clinical significance of KIT overexpression that associates with KIT gain-of-function mutations occurring in subsets of acute myeloid leukemia (AML) is unknown. At first, authors indicated Sp1/NFκB modulated KIT expression in AML. By EMSA and ChIP assay showed Sp1/NFκB binding on the KIT promoter region. When knockdown or overexpress Sp1 and NFκB(p65) that could downregulation or upregulation KIT expression level. They also found that miR-29b regulated KIT expression by Sp1. To treated Botezomib (proteasome inhibitor), Bay11-7082 (NFκB inhibitor) and Mithramycin A (Sp1 inhibitor) in Kasumi-1 cell, all of those compounds upregulated miR29b and decreased Sp1, Previously studies proved that Sp1/ NFκB interact with histone descetylases (HDACs) 1 and 3 to repress target gene transcription. Therefore, the decreased binding of HDACs on the miR-29b enhancer region was likely due to the disruption of the Sp1/HADC interaction by HDAC inhibitor. Finally, treatment with Bortezomib suppressed in vivo KIT-driven leukemogesis. Collectively, these results indicate that KIT overexpression significantly contributes to malignant cell proliferation, and targeting KIT abundance  through the miRNA protein network represents a promising therapeutic approach to overcome KIT-driven leukemia.

 

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