OTUD7B在急性髓系白血病细胞中的功能及机制

Function of OTUD7B in acute myeloid leukemia cells and its mechanism

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/m TOR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m TOR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/m TOR信号通路的活化有关。

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 kasumil, 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. OTUDTB overexpression in HL60 and kastmail 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 kasumil cells and the entry of cells into S phase. The inhibitory effect of OTUD7B overexpression on AML ceils might be related to the inhibition ofAKT / mTOR signaling pathway.