ZC3H13 facilitates the progression of acute myeloid leukemia through m6A-FOXP1-mediated metabolic reprogramming

Acute myeloid leukemia (AML) is a complex hematologic malignancy characterized by rapid progression and high relapse rates. Zinc finger CCCH domain-containing protein 13 (ZC3H13) has been implicated in the pathogenesis of various diseases, but its role in AML remains unclear. This study aimed to elucidate the function and underlying mechanisms of ZC3H13 in AML. Gene expression patterns and correlations with patient survival were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database. ZC3H13 expression was quantified in AML bone marrow samples and cell lines via real-time reverse-transcription PCR (qRT-PCR) and Western blotting. Cell proliferation was assessed using Cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays, whereas flow cytometry was employed to evaluate cell cycle progression, apoptosis, and reactive oxygen species (ROS) levels. Glycolytic activity-including glucose consumption, lactate production, and ATP levels-was measured using commercial kits. Oxidative stress markers such as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) were also quantified. The LinkedOmics database was used to identify ZC3H13-associated genes and predict their functional correlations. Potential m6A modification sites on FOXP1 mRNA were predicted using the SRAMP tool and validated through methylated RNA immunoprecipitation (MeRIP) assays. A dual-luciferase reporter assay confirmed direct binding of ZC3H13 to the FOXP1 promoter. ZC3H13 was found to be highly expressed in AML bone marrow and cell lines. Functionally, ZC3H13 promoted cell proliferation, enhanced glycolysis, and suppressed both apoptosis and oxidative stress. Mechanistically, ZC3H13 stabilized FOXP1 expression via m6A methylation, thereby contributing to AML progression. In conclusion, ZC3H13 accelerates AML development by modulating the m6A-FOXP1 axis, leading to metabolic reprogramming. These findings provide novel insights into AML pathogenesis and offer potential targets for therapeutic intervention.