TRAF7 inhibits glycolysis to potentiate growth inhibition and apoptosis of myeloid leukemia cells via regulating the KLF2-PFKFB3 axis
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, TRA...
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Elsevier
2023-06-01
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| Series: | Molecular and Cellular Probes |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0890850823000208 |
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| author | Lin Zou Ye Fang Wei He |
| author_facet | Lin Zou Ye Fang Wei He |
| author_sort | Lin Zou |
| collection | DOAJ |
| description | 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. |
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| id | doaj.art-f3b9f77c5fa54325953db7573940cebe |
| institution | Directory Open Access Journal |
| issn | 0890-8508 |
| language | English |
| last_indexed | 2024-03-13T01:37:23Z |
| publishDate | 2023-06-01 |
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| series | Molecular and Cellular Probes |
| spelling | doaj.art-f3b9f77c5fa54325953db7573940cebe2023-07-04T05:09:10ZengElsevierMolecular and Cellular Probes0890-85082023-06-0169101911TRAF7 inhibits glycolysis to potentiate growth inhibition and apoptosis of myeloid leukemia cells via regulating the KLF2-PFKFB3 axisLin Zou0Ye Fang1Wei He2Priority Medical Department, General Hospital of Central Theater Command, Wuhan, 430070, Hubei, ChinaPriority Medical Department, General Hospital of Central Theater Command, Wuhan, 430070, Hubei, ChinaCorresponding author. Priority Medical Department, General Hospital of Central Theater Command, No. 627 of Wuluo Road, Wuchang District, Wuhan, 430070, Hubei Province, China.; Priority Medical Department, General Hospital of Central Theater Command, Wuhan, 430070, Hubei, ChinaTumor 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.http://www.sciencedirect.com/science/article/pii/S0890850823000208TRAF7Acute myeloid leukemiaKLF2PFKFB3Glycolysis |
| spellingShingle | Lin Zou Ye Fang Wei He TRAF7 inhibits glycolysis to potentiate growth inhibition and apoptosis of myeloid leukemia cells via regulating the KLF2-PFKFB3 axis Molecular and Cellular Probes TRAF7 Acute myeloid leukemia KLF2 PFKFB3 Glycolysis |
| title | TRAF7 inhibits glycolysis to potentiate growth inhibition and apoptosis of myeloid leukemia cells via regulating the KLF2-PFKFB3 axis |
| title_full | TRAF7 inhibits glycolysis to potentiate growth inhibition and apoptosis of myeloid leukemia cells via regulating the KLF2-PFKFB3 axis |
| title_fullStr | TRAF7 inhibits glycolysis to potentiate growth inhibition and apoptosis of myeloid leukemia cells via regulating the KLF2-PFKFB3 axis |
| title_full_unstemmed | TRAF7 inhibits glycolysis to potentiate growth inhibition and apoptosis of myeloid leukemia cells via regulating the KLF2-PFKFB3 axis |
| title_short | TRAF7 inhibits glycolysis to potentiate growth inhibition and apoptosis of myeloid leukemia cells via regulating the KLF2-PFKFB3 axis |
| title_sort | traf7 inhibits glycolysis to potentiate growth inhibition and apoptosis of myeloid leukemia cells via regulating the klf2 pfkfb3 axis |
| topic | TRAF7 Acute myeloid leukemia KLF2 PFKFB3 Glycolysis |
| url | http://www.sciencedirect.com/science/article/pii/S0890850823000208 |
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