Knocking-down cyclin A(2) by siRNA suppresses apoptosis and switches differentiation pathways in K562 cells upon administration with doxorubicin.
Knocking-down cyclin A(2) by siRNA suppresses apoptosis and switches differentiation pathways in K562 cells upon administration with doxorubicin.
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DOI：
10.1371/journal.pone.0006665
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发表时间：
2009-08-17
期刊：
影响因子：
3.7
通讯作者：
Qu X
中科院分区：
文献类型：
--
作者：
Wang X;Song Y;Ren J;Qu X
细胞周期蛋白A2对于DNA复制、转录和细胞周期调控的起始至关重要。越来越多的证据表明，细胞周期蛋白A2的失调与染色体不稳定性、肿瘤转化和肿瘤增殖密切相关。在这里，我们报道用阿霉素治疗慢性髓性白血病K562细胞导致细胞周期蛋白A2的积累，随后诱导凋亡细胞死亡。为了研究潜在的临床前相关性，我们通过功能化的单壁碳纳米管将靶向细胞周期蛋白A2的siRNA瞬时转染K562细胞。敲低K562细胞中cyclin A2的表达可抑制阿霉素诱导的生长停滞和细胞凋亡。给予阿霉素后，细胞周期蛋白A2减少的K562细胞红细胞分化明显减少，小部分细胞沿巨核细胞和单核-巨噬细胞途径分化。结果证实了细胞周期蛋白A2的促凋亡作用，提示细胞周期蛋白A2是细胞分化的关键调节因子。据我们所知，这是首次报道敲低一个基因的表达可以改变人类髓性白血病K562细胞的分化途径。
Cyclin A2 is critical for the initiation of DNA replication, transcription and cell cycle regulation. Cumulative evidences indicate that the deregulation of cyclin A2 is tightly linked to the chromosomal instability, neoplastic transformation and tumor proliferation. Here we report that treatment of chronic myelogenous leukaemia K562 cells with doxorubicin results in an accumulation of cyclin A2 and follows by induction of apoptotic cell death. To investigate the potential preclinical relevance, K562 cells were transiently transfected with the siRNA targeting cyclin A2 by functionalized single wall carbon nanotubes. Knocking down the expression of cyclin A2 in K562 cells suppressed doxorubicin-induced growth arrest and cell apoptosis. Upon administration with doxorubicin, K562 cells with reduced cyclin A2 showed a significant decrease in erythroid differentiation, and a small fraction of cells were differentiated along megakaryocytic and monocyte-macrophage pathways. The results demonstrate the pro-apoptotic role of cyclin A2 and suggest that cyclin A2 is a key regulator of cell differentiation. To the best of our knowledge, this is the first report that knocking down expression of one gene switches differentiation pathways of human myeloid leukemia K562 cells.
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影响因子：
11.2
作者：
Chen, W;Lee, JW;Fine, HA
通讯作者：
Fine, HA
DOI：
10.1073/pnas.0707654105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Liu, Zhuang;Davis, Corrine;Dai, Hongjie
通讯作者：
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影响因子：
3.5
作者：
Ito, Y;Takeda, T;Matsuura, N
通讯作者：
Matsuura, N
影响因子：
8.8
作者：
Huuhtanen, RL;Wiklund, TA;Andersson, LC
通讯作者：
Andersson, LC
影响因子：
4.8
作者：
Meikrantz, W;Schlegel, R
通讯作者：
Schlegel, R