Knockdown of SPAG6 regulates triglyceride metabolism via the P38 MAPK/ERK/PPARα axis in acute myeloid leukemia

Numerous studies have already revealed that the development of acute myeloid leukemia (AML) is closely related to the dysregulation of lipid metabolism. The aim of this study was to elucidate the biological role and molecular mechanisms of Sperm Associated Antigen 6(SPAG6) in AML. Our research found that the expression level of SPAG6 was significantly elevated in clinical samples of AML compared to normal samples. Meanwhile, the expression of carnitine palmitoyltransferase 1 A (CPT1A), a marker associated with lipid accumulation, also showed an upward trend. Lentivirus knock-downing SPAG6 was used to investigate the tumorigenic phenotypes of AML.The results indicated that knockdown of SPAG6 increased lipid accumulation both in vivo and in vitro by downregulating the expression of fatty acid oxidation (FAO)-related genes, thereby slowing the progression of the disease. Furthermore, PPARα was found to upregulate the expression of FAO-related genes through activation of the P38 MAPK/ERK pathway, thereby promoting tumor development. Our study uncovers a novel function of SPAG6 in lipid metabolism via the P38 MAPK/ERK/PPARα axis, providing new theoretical insights into the pathogenesis of AML. Targeting SPAG6 may emerge as a potential strategy for AML treatment.