Zhao Lei, Zhu Cui-Min, Zhang Zhi-Hua, Tian Wen-Liang, Hao Chang-Lai
Department of Hematology, Affiliated Hospital of Chengde Medical Collge, Chengde 067000, Hebei Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Apr;17(2):363-7.
This study was aimed to investigate the mechanism of histone deacetylase (HDAC) inhibitor, valproic acid (VPA), reversing transcription inhibition of AML1-ETO fusion protein in Kasumi-1 cell line. The mRNA expressions of AML1-ETO, AML1 and cyclin D2 were detected by semi-quantitation RT-PCR after treating kasumi-1 cells with VPA at different doses/and different time points. The results indicated that the mRNA expression of AML1-ETO showed no obvious change, when kasumi-1 cells were treated with VPA. Compared with control group, the expression level of AML1 mRNA significantly increased in a dose-dependent manner. Compared with control group, the expression level of cyclin D2 mRNA significantly decreased when kasumi-1 cells had been treated with 3 mmol/L VPA as well as kasumi-1 cells were treated with different concentrations of VPA for 3 days. In conclusion, VPA could remove transcription inhibition of AML1-ETO fusion protein, increase transcription of AML1 and down-regulate mRNA expression of AML1 target gene cyclin D2 through HDAC inhibiting activity.
本研究旨在探讨组蛋白去乙酰化酶(HDAC)抑制剂丙戊酸(VPA)逆转Kasumi-1细胞系中AML1-ETO融合蛋白转录抑制的机制。在不同剂量/不同时间点用VPA处理Kasumi-1细胞后,通过半定量RT-PCR检测AML1-ETO、AML1和细胞周期蛋白D2的mRNA表达。结果表明,用VPA处理Kasumi-1细胞时,AML1-ETO的mRNA表达无明显变化。与对照组相比,AML1 mRNA的表达水平呈剂量依赖性显著增加。与对照组相比,当Kasumi-1细胞用3 mmol/L VPA处理以及用不同浓度的VPA处理3天时,细胞周期蛋白D2 mRNA的表达水平显著降低。总之,VPA可通过HDAC抑制活性消除AML1-ETO融合蛋白的转录抑制,增加AML1的转录并下调AML1靶基因细胞周期蛋白D2的mRNA表达。