Abstract

Triple-negative breast cancer (TNBC) is highly malignant with rising incidence and mortality. Solute carrier family 7 member 5 ( SLC7A5 ) is an amino acid transporter, and its mechanism in TNBC is still unclear. The public databases (TIMER2.0, TCGA, GEPIA, Kaplan-Meier Plotter, linkedomics, RBPmap, and RBPDB) were used to analyze the expression and correlation of genes and prognosis correlation. Gene and protein expression was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. 3-(4, 5)-Dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide (MTT), terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) staining, flow cytometry, transwell, sphere/tube formation, and metabolic kits were used to assess cell viability, apoptosis, invasion, stemness, angiogenesis, and glutamine (Gln) metabolism. The binding of forkhead box M1 ( FOXM1 ) to the SLC7A5 promoter was determined by dual-luciferase reporter assay/chromatin immunoprecipitation (ChIP). RNA binding protein immunoprecipitation (RIP), RNA pull-down, and actinomycin D (Act D) experiments evaluated fused in sarcoma ( FUS )- SLC7A5 interaction. In vivo, the mouse xenografts were established to validate the effects of FOXM1 / SLC7A5 axis. Hematoxylin-eosin (HE) and immunohistochemistry (IHC) assays were used for histological morphology analysis and the protein expression of Ki67 and SLC7A5. SLC7A5 was up-regulated in TNBC and correlated with poor prognosis. Its knockdown repressed TNBC cell viability, invasion, stemness, angiogenesis, and Gln metabolism (as evidenced by reduced Gln, α-ketoglutarate (α-KG), and adenosine 5’-triphosphate (ATP) levles). FOXM1 transcriptionally activated SLC7A5 ; SLC7A5 overexpression reversed the suppressive effects of FOXM1 knockdown on TNBC malignancy and metabolism. Additionally, FUS bound to and stabilized SLC7A5 mRNA . In vivo, SLC7A5 counteracted the FOXM1 knockdown-mediated in