摘要/Abstract
摘要： 目的· 探讨OTUD7B 在急性髓系白血病（acute myeloid leukemia，AML）细胞中的生物学效应与作用机制。方法· 检测
AML 患者外周血单个核细胞中OTUD7B 基因的表达和AML 患者骨髓单个核细胞中OTUD7B 蛋白的表达。利用TCGA 数据库验证
OTUD7B 与AML 患者生存期的关系。构建M2 型AML 小鼠模型，检测模型小鼠骨髓、脾脏和肝脏中OTUD7B 的表达。在白血病
细胞株HL60 和kasumi1 中过表达OTUD7B，检测OTUD7B 蛋白对细胞活率及细胞周期的影响；在稳定表达OTUD7B 的HL60 和
kasumi1 细胞株中，检测AKT/mTOR 通路蛋白的变化；过表达AKT1 后检测OTUD7B 引起的细胞生长抑制的变化。结果· OTUD7B
在各个类型AML 患者原代细胞中表达量均较低。OTUD7B 表达量与AML 患者的生存期密切相关。与野生型小鼠比较，M2 型
AML 小鼠骨髓、肝脏及脾脏中OTUD7B 的表达量均较低。HL60 和kasumi1 细胞中过表达OTUD7B 能够显著抑制细胞活率，降
低S 期细胞的比例，并显著抑制AKT 和mTOR 蛋白的磷酸化；过表达AKT1 后能够部分逆转OTUD7B 对细胞的生长抑制作用。结
论· OTUD7B 在原代AML 患者细胞及M2 型AML 小鼠的骨髓、肝脏和脾脏中低表达，并且OTUD7B 表达量低的患者生存期更短。
OTUD7B 过表达能明显抑制AML 细胞HL60 和kasumi1 的细胞活率，并且显著抑制细胞进入S 期。OTUD7B 过表达对AML 细胞的
抑制效应可能与抑制AKT/mTOR 信号通路的活化有关。
关键词: OTUD7B, 急性髓系白血病, 增殖抑制, AKT/mTOR 信号通路
Abstract:
Objective · To investigate the biological effect and mechanism of OTUD7B in acute myeloid leukemia (AML) cells. Methods · The expression
of OTUD7B in peripheral blood mononuclear cells and bone marrow mononuclear cells of AML patients were detected. The relationship between OTUD7B
and survival of AML patients was confirmed by using TCGA database. Mouse model of M2 type AML was established, and the expression of OTUD7B in
the bone marrow, spleen and liver of the mice was detected. OTUD7B was overexpressed in AML cell lines HL60 and kasumi1, then the cell viability and
cell cycle were measured. The AKT/mTOR pathway proteins were detected after OTUD7B overexpressed and then the cell growth inhibition was detected
after overexpression of AKT1. Results · The expression of OTUD7B was lower in primary leukemia cells from all types of AML patients and in the bone
marrow, liver and spleen of M2 type AML mice, which was closely related to the survival time of AML patients. OTUD7B overexpression in HL60 and
kasumi1 cells significantly inhibited the cell viability and decreased the percentage of S phase cells. OTUD7B significantly inhibited the phosphorylation of
AKT and mTOR, and AKT1 overexpression partially reversed the inhibitory effect of OTUD7B on cell growth. Conclusion · OTUD7B expression is low in
primary leukemia cells from AML patients and in bone marrow, liver and spleen of the M2 type AML mice. The survival time of patients with low OTUD7B
expression is shorter. Overexpression of OTUD7B significantly inhibited the cell viability of HL60 and kasumi1 cells and the entry of cells into S phase. The
inhibitory effect of OTUD7B overexpression on AML cells might be related to the inhibition of AKT / mTOR signaling pathway.
Key words: OTUD7B, acute myeloid leukemia, proliferation inhibition, AKT/mTOR signaling pathway
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