TRAF7 inhibits glycolysis to potentiate growth inhibition and apoptosis of myeloid leukemia cells via regulating the KLF2-PFKFB3 axis

IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS
Lin Zou, Ye Fang, Wei He
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Abstract

Tumor necrosis factor receptor-related factor 7 (TRAF7) can regulate cell differentiation and apoptosis, but its specific functional mechanism in the pathological process of acute myeloid leukemia (AML) closely related to differentiation and apoptosis disorders is largely unclear. In this study, TRAF7 was found to be lowly expressed in AML patients and a variety of myeloid leukemia cells. TRAF7 was overexpressed in AML Molm-13 and chronic myeloid leukemia (CML) K562 cells by transfection with pcDNA3.1-TRAF7. CCK-8 assay and flow cytometry analysis showed that TRAF7 overexpression induced growth inhibition and apoptosis in K562 and Molm-13 cells. Measurements of glucose and lactate suggested that TRAF7 overexpression impaired glycolysis of K562 and Molm-13 cells. Cell cycle analysis indicated that most of K562 and Molm-13 cells were captured in G0/G1 phase by TRAF7 overexpression. PCR and western blot assay revealed that TRAF7 increased Kruppel-like factor 2 (KLF2) expression but decreased 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) expression in AML cells. KLF2 knockdown can counteract TRAF7-triggered PFKFB3 inhibition, and abolish TRAF7-mediated glycolysis inhibition and cell cycle arrest. KLF2 knockdown or PFKFB3 overexpression both can partially neutralize TRAF7-induced growth inhibition and apoptosis of K562 and Molm-13 cells. Moreover, Lv-TRAF7 decreased human CD45+ cells in mouse peripheral blood in the xenograft mice established by NOD/SCID mice. Taken together, TRAF7 exerts anti-leukemia effects by impairing glycolysis and cell cycle progression of myeloid leukemia cells via modulating the KLF2-PFKFB3 axis.

TRAF7通过调节KLF2-PFKFB3轴抑制糖酵解增强髓系白血病细胞的生长抑制和凋亡
肿瘤坏死因子受体相关因子7(TRAF7)可以调节细胞分化和凋亡,但其在急性髓系白血病(AML)病理过程中的具体功能机制与分化和凋亡障碍密切相关,目前尚不清楚。在这项研究中,发现TRAF7在AML患者和各种髓系白血病细胞中低表达。通过用pcDNA3.1-TRAF7转染,TRAF7在AML Molm-13和慢性粒细胞白血病(CML)K562细胞中过表达。CCK-8测定和流式细胞术分析显示TRAF7过表达诱导K562和Molm-13细胞的生长抑制和凋亡。葡萄糖和乳酸的测量表明TRAF7过表达损害了K562和Molm-13细胞的糖酵解。细胞周期分析表明,TRAF7过表达使K562和Molm-13细胞大多处于G0/G1期。PCR和蛋白质印迹分析显示TRAF7增加了AML细胞中Kruppel样因子2(KLF2)的表达,但降低了6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶3(PFKFB3)的表达。KLF2敲低可以抵消TRAF7触发的PFKFB3抑制,并消除TRAF7介导的糖酵解抑制和细胞周期停滞。KLF2敲低或PFKFB3过表达都可以部分中和TRAF7诱导的K562和Molm-13细胞的生长抑制和凋亡。此外,在由NOD/SCID小鼠建立的异种移植物小鼠中,Lv-TRAF7降低了小鼠外周血中的人CD45+细胞。总之,TRAF7通过调节KLF2-PFKFB3轴来损害髓系白血病细胞的糖酵解和细胞周期进展,从而发挥抗白血病作用。
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来源期刊
Molecular and Cellular Probes
Molecular and Cellular Probes 生物-生化研究方法
CiteScore
6.80
自引率
0.00%
发文量
52
审稿时长
16 days
期刊介绍: MCP - Advancing biology through–omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.
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