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

• Published in: Molecular and cellular probes Vol. 69; p. 101911
• Main Authors: Zou, Lin, Fang, Ye, He, Wei
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2023; Elsevier
• Subjects: Acute myeloid leukemia; Animals; Apoptosis - genetics; Cell Line, Tumor; Cell Proliferation - genetics; Glycolysis; Glycolysis - genetics; Humans; KLF2; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Kruppel-Like Transcription Factors - pharmacology; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Mice; Mice, Inbred NOD; Mice, SCID; PFKFB3; Phosphofructokinase-2 - metabolism; Phosphofructokinase-2 - pharmacology; Phosphoric Monoester Hydrolases - metabolism; TRAF7; Transcription Factors - metabolism; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins - metabolism; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins - pharmacology; AML; TRAF7; LDHA; PFKFB3; PKM2; MEKK3; Glycolysis; Acute myeloid leukemia; GLUT5; KLF2; HK2
• ISSN: 0890-8508; 1096-1194
• DOI: 10.1016/j.mcp.2023.101911

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 induces growth inhibition and apoptosis of AML cells.•TRAF7 impairs glycolysis and cell cycle progression of AML cells.•TRAF7 potentiates KLF2-mediated PFKFB3 inhibition in AML cells.•KLF2 inhibition or PFKFB3 overexpression restores the anti-leukemia effects of TRAF7.