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

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



    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.


1. Felli, N., Fontana, L., Pelosi, E., Botta, R., Bonci, D., Facchiano, F., Liuzzi, F., Lulli, V., Morsilli, O., Santoro, S., et al. (2005). MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor downmodulation. Proc. Natl. Acad. Sci. USA 102, 18081–18086.


2. Liu, S., Liu, Z., Xie, Z., Pang, J., Yu, J., Lehmann, E., Huynh, L., Vukosavljevic, T., Takeki, M., Klisovic, R.B., et al. (2008). Bortezomib induces DNA hypomethylation and silenced gene transcription by interfering with Sp1/NF-kappaB-dependent DNA methyltransferase activity in acute myeloid leukemia. Blood 111, 2364–2373.