Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
Acta Haematol. 2012;128(1):39-46. doi: 10.1159/000337418. Epub 2012 May 17.
BACKGROUND/AIMS: The degradation of mRNA is a key process in the control of gene expression correlated to anomalous cell proliferation. The rate-limiting step of mRNA degradation is the removal of the poly(A) tail by deadenylases. However, studies on deadenylase expression in cancer are limited. Herein, we analyzed the expression of several deadenylases from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).
Clinical samples from patients diagnosed with ALL and AML were the source of leukemic cells. Extracts from leukemic and control cells were analyzed for deadenylase mRNA levels using qRT-PCR, and the protein levels of PARN and CNOT7 deadenylases using immunoblotting.
RT-PCR analysis revealed altered expression for CNOT6, CNOT6L, CNOT7 and PARN deadenylases. The most significant alterations were observed for PARN and CNOT7 mRNA levels, which also reflect on the cognate protein level. Further analysis revealed that a significant amount of PARN is phosphorylated in ALL.
We show that the expression of several deadenylases in acute leukemias is altered. The increase of PARN expression and the alteration of its phosphorylation status indicate important regulatory events. These data suggest that the role of deadenylases as auxiliary biomarkers and therapeutic targets should be meticulously investigated.
背景/目的：mRNA 的降解是与异常细胞增殖相关的基因表达调控的关键过程。mRNA 降解的限速步骤是由脱腺苷酶去除 poly(A)尾巴。然而，关于癌症中脱腺苷酶表达的研究有限。在此，我们分析了急性淋巴细胞白血病 (ALL) 和急性髓细胞白血病 (AML) 中几种脱腺苷酶的表达。
从诊断为 ALL 和 AML 的患者的临床样本中获得白血病细胞。使用 qRT-PCR 分析白血病和对照细胞提取物中的脱腺苷酶 mRNA 水平，并使用免疫印迹法分析 PARN 和 CNOT7 脱腺苷酶的蛋白水平。
RT-PCR 分析显示 CNOT6、CNOT6L、CNOT7 和 PARN 脱腺苷酶的表达发生改变。PARN 和 CNOT7 mRNA 水平的变化最为显著，这也反映在相应的蛋白水平上。进一步的分析表明，ALL 中有相当数量的 PARN 发生了磷酸化。
我们表明急性白血病中几种脱腺苷酶的表达发生了改变。PARN 表达的增加及其磷酸化状态的改变表明存在重要的调节事件。这些数据表明，脱腺苷酶作为辅助生物标志物和治疗靶点的作用应仔细研究。
