微小染色体维持蛋白8在慢性粒细胞白血病中的表达
Expression of minichromosome maintenance 8 in chronic myelogenous leukemia.
作者信息
Cai Lili, Zhao Kai, Yuan Xuejie
机构信息
Department of Blood Transfusion, The First People's Hospital of Shangqiu City Shangqiu 476000, Henan Province, P. R. China.
Department of Clinical Laboratory, The First People's Hospital of Shangqiu City Shangqiu 476000, Henan Province, P. R. China.
出版信息
Int J Clin Exp Pathol. 2015 Nov 1;8(11):14180-8. eCollection 2015.
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.
目的
微小染色体维持蛋白8（MCM8）被鉴定为一种起始解旋酶，参与DNA延伸并与癌症相关。然而，关于MCM8在慢性粒细胞白血病（CML）中的作用知之甚少。我们旨在探讨MCM8在CML中的表达及作用。
方法
从6例CML患者和3名健康个体中制备外周血单个核细胞（PBMC）和骨髓单个核细胞（BMMC）。测定并比较MCM8的mRNA水平。采用小干扰RNA（siRNA）方法沉默人CML细胞系K562中MCM8的表达。转染MCM8 siRNA后，分析细胞活力和凋亡率，以及半胱天冬酶-3（Caspase-3）和B细胞淋巴瘤（Bcl）-xL的蛋白表达水平。
结果
CML患者PBMC和BMMC中MCM8的相对mRNA水平均显著高于健康个体（P < 0.05）。与对照组或乱序siRNA组相比，敲低MCM8可使细胞活力显著降低，而凋亡率则有统计学意义的增加（均P < 0.05）。此外，与对照组或乱序siRNA组相比，Caspase-3的蛋白表达水平显著升高（P < 0.05），而Bcl-xL的水平则有统计学意义的降低（P < 0.05）。
结论
MCM8在CML中起重要作用，敲低MCM8可能是CML一种潜在的靶向治疗方法。
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