Prognostic and functional significance of SLC7A11 and its relationship with the proliferation and apoptosis of acute myeloid leukaemia cells

Abstract

Abstract Purpose: Acute myeloid leukaemia (AML) is a common type of leukaemia in adults. Solute carrier family 7 member 11 (SLC7A11) may be a therapeutic target for multiple cancer types. However, the effects and action mechanism of SLC7A11 in AML remain unknown. Here, we investigated the prognostic and functional significance of SLC7A11 in AML. Methods: We performed Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction network, immune cell infiltration, transcription factor-miRNA–mRNA regulatory network, mutation, and methylation analyses. Results: SLC7A11 was significantly upregulated in most tumours, including AML, and correlated with a poor overall survival. A comparison of the high and low SLC7A11 expression groups revealed 1184 differentially expressed genes and 699 genes co-expressed with SLC7A11. The KEGG pathway enrichment analysis revealed their involvement in the Rap1 signalling pathway. The immune infiltration analysis indicated that SLC7A11 expression correlated with the infiltration levels of eosinophils and naïve B, plasma B, CD8+ T, CD4+ memory activated, resting and activated natural killer, and resting myeloid dendritic cells. The regulatory network indicated that GATA1 and has-miR-143-3pmay be upstream regulators of SLC7A11. The methylation levels of seven CpG sites were found to be associated with prognosis using the MethSurv database. In vitro experiments showed that erastin, an SLC7A11 inhibitor, inhibited cell proliferation, prolonged the G1 phase, and shortened the S phase, whilst daunorubicin had a synergistic effect on the inhibition of AML cell (U937 and THP1) proliferation. Conclusion: These findings indicate that SLC7A11 is a potential therapeutic target for AML, which may be regulated by the GATA1- has-miR-143-3p -SLC7A11network and the RAP1 signaling pathway.