Expression of minichromosome maintenance 8 in chronic myelogenous leukemia.
Expression of minichromosome maintenance 8 in chronic myelogenous leukemia.
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DOI：
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发表时间：
2015-11
影响因子：
1.4
通讯作者：
L. Cai;K. Zhao;Xuejie Yuan
中科院分区：
文献类型：
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作者：
L. Cai;K. Zhao;Xuejie Yuan
微小染色体维持8（MCM 8）被鉴定为参与DNA延伸和参与癌症的起始解旋酶。然而，关于MCM 8在慢性粒细胞白血病（CML）中的作用的信息很少。本研究旨在探讨MCM 8在慢性粒细胞白血病（CML）中的表达及其作用。方法分别从6例CML患者和3例健康人外周血单个核细胞（PBMC）和骨髓单个核细胞（BMMC）中分离培养。测定并比较MCM 8的mRNA水平。应用小干扰RNA（siRNA）技术沉默人CML细胞系K562中MCM 8的表达。转染MCM 8 siRNA后，检测细胞存活率和凋亡率，以及Caspase-3和B细胞淋巴瘤（Bcl）-xL蛋白表达水平。结果CML患者PBMC和BMMC中MCM 8的相对mRNA水平均显著高于正常对照组（P < 0.05）。与对照组或scramble siRNA组相比，MCM 8基因敲低组细胞存活率显著降低，而凋亡率显著增加（均P < 0.05）。与对照组和scramble siRNA组相比，Caspase-3蛋白表达水平显著升高（P < 0.05），Bcl-xL蛋白表达水平显著降低（P < 0.05）。结论MCM 8在CML发病中起重要作用，MCM 8基因敲除可能成为CML治疗的靶向药物。
OBJECTIVES Minichromosome maintenance 8 (MCM8) is identified as an initiating helicase involved in DNA elongation and involved in cancer. However, little information is available for the role of MCM8 on chronic myelogenous leukemia (CML). We aimed to explore the expression and effect of MCM8 on CML. METHODS Peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) were prepared from six patients with CML and three healthy individuals. The mRNA levels of MCM8 were determined and compared. The expression of MCM8 was silenced by small interfering RNA (siRNA) approach in human CML cell line K562. After transfection with MCM8 siRNA, cell viability and apoptotic rate were analyzed, as well as the protein expression levels of Caspase-3 and B-cell lymphoma (Bcl)-xL. RESULTS Relative mRNA levels of MCM8 were both significantly higher in PBMC and BMMC from CML patients than those in healthy individuals (P < 0.05). The cell viability was significantly reduced while the apoptotic rate was statistically increased by knockdown of MCM8 compared to control group or the scramble siRNA group (both P < 0.05). Moreover, the protein expression levels of Caspase-3 were significantly increased (P < 0.05), and while the levels of Bcl-xL were statistically reduced (P < 0.05) compared to the control group or the scramble siRNA group. CONCLUSION MCM8 plays a significant role in CML, and knockdown of MCM8 might be a potentially targeted therapy for CML.