Xiao Han, Cheng Qian, Wu Xinyu, Tang Yishu, Liu Jing, Li Xin
Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Cancer Manag Res. 2019 Sep 20;11:8547-8555. doi: 10.2147/CMAR.S210504. eCollection 2019.
Acute myeloid leukemia (AML) is the most common type of leukemia and characterized by the malignant growth of leukemic cells. Adenosine deaminases acting on RNA 1 (ADAR1) have been shown to participate in the proliferation of cancer cells and progression of various cancers. However, the role of ADAR1 in AML has not been investigated.
We compared the expression levels of ADAR1 between samples obtained from different AML patients and controls using quantitative-polymerase chain reaction and Western blotting. We also investigated the functional role and possible mechanisms via silencing the expression of ADAR1 in vitro and in vivo.
We found that the mRNA and protein levels of ADAR1 were significantly higher in AML patients. The mRNA expression of ADAR1 was positively correlated with the ratio of leukemic cells. Additionally, silencing of ADAR1 expression significantly suppressed the proliferation of AML cells and induced G0/1 arrest. For the analysis of the mechanism, the quantitative-polymerase chain reaction and Western blotting results revealed that ADAR1 knockdown resulted in the decreased expression of Wingless-Int (Wnt) effectors including β-catenin, c-Myc, transcription factor 4, and cyclin D2. In the nude mouse model, inhibition of ADAR1 expression reduced the tumorigenic potential and decreased the expression o]f Wnt effectors.
These results demonstrate that ADAR1 may be involved in the regulation of the proliferation of AML cells partially via regulation of the Wnt signaling pathway.
急性髓系白血病（AML）是最常见的白血病类型，其特征为白血病细胞的恶性增殖。作用于RNA的腺苷脱氨酶1（ADAR1）已被证明参与癌细胞增殖及多种癌症的进展。然而，ADAR1在AML中的作用尚未得到研究。
我们使用定量聚合酶链反应和蛋白质免疫印迹法，比较了来自不同AML患者及对照的样本中ADAR1的表达水平。我们还通过在体外和体内沉默ADAR1的表达，研究了其功能作用及可能机制。
我们发现AML患者中ADAR1的mRNA和蛋白质水平显著更高。ADAR1的mRNA表达与白血病细胞比例呈正相关。此外，沉默ADAR1表达显著抑制了AML细胞的增殖并诱导G0/1期阻滞。对于机制分析，定量聚合酶链反应和蛋白质免疫印迹结果显示，敲低ADAR1导致包括β-连环蛋白、c-Myc、转录因子4和细胞周期蛋白D2在内的无翅型MMTV整合位点家族（Wnt）效应分子的表达降低。在裸鼠模型中，抑制ADAR1表达降低了致瘤潜能并降低了Wnt效应分子的表达。
这些结果表明，ADAR1可能部分通过调节Wnt信号通路参与AML细胞增殖的调控。
