KLF8 enhances acute myeloid leukemia cell growth and glycolysis via AKT/mTOR pathway

Purpose: To determine the role and mechanisms of Kruppel-like transcription factor 8 (KLF8) in acute myeloid leukemia (AML). Methods: The transcriptional and translational levels of KLF8 in AML cell lines were determined by quantitative real time-polymerase chain reaction (qRT-PCR) and western blotting. Two RNAs targeting KLF8 were transfected into KG-1 and HL-60 cells. The growth and apoptosis of AML cells were determined using CCK-8, 5-ethynyl-2-deoxyuridine (EdU), flow cytometry, and western blot assays. Glycolysis was evaluated by relative glucose consumption, lactate generation, ATP levels, and hexokinase II (HK2), while glucose transporter 1 (GLUT1) protein expression levels. AKT, phosphorylated AKT (p-AKT), mammalian target of rapamycin (mTOR), and p-mTOR expression levels were assessed by western blot. Results: KLF8 mRNA and protein expression levels were elevated in AML cells (p < 0.01). KLF8 knockdown in AML cells decreased cell viability, EdU-positivity, relative glucose consumption, lactate generation, ATP levels, and HK2 and GLUT1 protein levels (p < 0.01). Apoptosis increased in KG-1 and HL-60 cells, with enhanced Bax and reduced Bcl-2 protein levels, after transfection with sh-KLF8. The relative expression levels of p-AKT/AKT and p-mTOR/mTOR were reduced in KG-1 and HL-60 cells transfected with sh-KLF8. Conclusion: Downregulation of KLF8 inhibits proliferation and glycolysis, and also promotes apoptosis in AML cells via AKT/mTOR pathway.