首页|节律分子BMAL2对急性髓系白血病细胞有氧糖酵解和细胞增殖的影响

节律分子BMAL2对急性髓系白血病细胞有氧糖酵解和细胞增殖的影响

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目的:了解类芳烃受体核转位蛋白2(BMAL2)在急性髓系白血病(AML)中的表达及与患者预后的关系,分析其对AML细胞有氧糖酵解和增殖的影响.方法:应用实时定量PCR法检测AML患者和正常对照组的骨髓单个核细胞中BMAL2的表达情况.利用美国国家生物技术信息中心公共数据库分析BMAL2表达与AML患者预后的相关性.通过慢病毒系统敲低AML细胞系HL-60和Kasumi-1中BMAL2的表达,葡萄糖摄取实验、乳酸含量实验、CCK-8法、细胞集落形成实验检测其对细胞糖代谢、细胞增殖的影响.结果:BMAL2 mRNA在AML中的表达水平显著高于正常对照组(P<0.01).BMAL2表达高的AML患者总生存时间较低表达患者明显缩短(P<0.05).敲低AML细胞系HL-60和Kasumi-1中的BMAL2后,细胞葡萄糖摄取减少,乳酸生成减少.RT-PCR及Western blot检测结果显示,BMAL2通过增强HIF1A的表达来促进AML细胞有氧糖酵解,进而促进细胞增殖.结论:BMAL2高表达于AML中,通过HIF1A增强AML细胞有氧糖酵解从而促进细胞增殖.
Effects of BMAL2 on Aerobic Glycolysis and Cell Proliferation in Acute Myeloid Leukemia Cells
Objective:To explore the expression of basic helix-loop-helix ARNT like 2(BMAL2)in acute myeloid leukemia(AML)patients and its correlation with prognosis,and analyze its effects on the aerobic glycolysis and proliferation of AML cells.Methods:The expressions of BMAL2 in bone marrow mononuclear cells(BMMCs)of AML patients and normal control group were detected by RT-qPCR.The correlation of BMAL2 expression with prognosis of AML patients was analyzed using public database of National Center for Biotechnology Information(NCBI).The interfering in BMAL2 expression of HL-60 and Kasumi-1 cells was performed using lentiviral vector-mediated shRNA.Cell glucose metabolism and proliferation were detected by using glucose uptake experiment,lactate content test,CCK-8 assay and cell colony formation test.Results:The expression level of BMAL2 mRNA in BMMCs of AML patients was significantly higher than normal control group(P<0.01).The overall survival time of AML patients with high expression of BMAL2 was significantly shorter than those with low expression of BMAL2(P<0.05).Knockdown of BMAL2 significantly reduced glucose uptake and lactate production in AML cell line HL-60 and Kasumi-1 cells.The results of RT-PCR and Western blot showed that BMAL2 promoted aerobic glycolysis by enhancing the expression of HIF1A in AML cells,thereby promoting cell proliferation.Conclusion:BMAL2 is highly expressed in AML patients,and promotes aerobic glycolysis by enhancing the expression of HIF1A,thereby promoting cell proliferation.

basic helix-loop-helix ARNT like 2glucose metabolismcell proliferationacute myeloid leukemia

贾卫静、牟佼、崔文静

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空军军医大学第一附属医院血液内科,陕西西安 710032

空军军医大学第二附属医院核医学科,陕西西安 710038

西安市中心医院血液病研究所,陕西西安 710003

空军军医大学第一附属医院病理科,陕西西安 710032

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类芳烃受体核转位蛋白2 糖代谢 细胞增殖 急性髓系白血病

陕西省自然科学基础研究计划陕西省自然科学基础研究计划

2015JM84792017JM8025

2024

中国实验血液学杂志
中国病理生理学会

中国实验血液学杂志

CSTPCD北大核心
影响因子:0.988
ISSN:1009-2137
年,卷(期):2024.32(2)
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