Suppression of CDK2 expression by siRNA induces cell cycle arrest and cell proliferation inhibition in human cancer cells

Suppression of CDK2 expression by siRNA induces cell cycle arrest and cell proliferation inhibition in human cancer cells
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DOI:
10.5483/bmbrep.2010.43.4.291
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发表时间:
2010-04-30
期刊:
影响因子:
3.8
通讯作者:
Zhong, Jiu-Chang
Zhong, Jiu-Chang
中科院分区:
生物学3区
文献类型:
--
作者:
Long, Xiang-E;Gong, Zhao-Hui;Zhong, Jiu-Chang

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细胞周期蛋白依赖性激酶2(Cyclin-dependent kinase 2,CDK 2)是丝氨酸/苏氨酸蛋白激酶家族的一员,它启动真核细胞周期的主要转换,是一个很有前途的肿瘤治疗靶点。本研究旨在通过抑制cdk 2基因表达来诱导细胞周期阻滞和细胞增殖抑制。我们构建了一系列能够在转染的人细胞中成功表达小干扰RNA(siRNA)的RNA干扰(RNAi)质粒。结果表明,含有siRNA编码序列的RNAi质粒在mRNA和蛋白水平上下调了人癌细胞cdk 2基因的表达。此外,我们发现细胞周期被阻滞在G 0 G1期,细胞增殖被不同的siRNA抑制。这些结果表明,通过RNA干扰抑制CDK 2活性可能是人类癌症基因治疗的有效策略。[BMB报告2010; 43(4):291-296]
Cyclin-dependent kinase 2 (CDK2) is a member of serine/threonine protein kinases, which initiates the principal transitions of the eukaryotic cell cycle and is a promising target for cancer therapy. The present study was designed to inhibit cdk2 gene expression to induce cell cycle arrest and cell proliferation suppression. Here, we constructed a series of RNA interference (RNAi) plasmids which can successfully express small interference RNA (siRNA) in the transfected human cells. The results showed that the RNAi plasmids containing the coding sequences for siRNAs down-regulated the cdk2 gene expression in human cancer cells at the mRNA and the protein levels. Furthermore, we found that the cell cycle was arrested at G0G1 phases and the cell proliferation was inhibited by different siRNAs. These results demonstrate that suppression of CDK2 activity by RNAi may be an effective strategy for gene therapy in human cancers. [BMB reports 2010; 43(4): 291-296]