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.
题目: 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.
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。.
Keywords: acute myeloid leukemia; basic helix-loop-helix ARNT like 2; cell proliferation; glucose metabolism.