ABCA8 inhibits breast cancer cell proliferation by regulating the AMP activated protein kinase/mammalian target of rapamycin signaling pathway

ATP-binding cassette (ABC) subfamily A member 8 (ABCA8) has been reported to play a vital role in cancer development. Our study aimed to explore the role and the molecular mechanism of ABCA8 in breast cancer (BC) progression. GSE65194, GSE15852, and GSE45827 datasets were used to identify differentially expressed genes (DEGs) in BC. The diagnosis and prognosis value were determined using ROC curve analysis and Kaplan-Meier plotter, respectively. The relationship between ABCA8 expression and clinicopathological features in BC was analyzed by TCGA. Co-expressed genes of ABCA8 in BC were screened out through GEPIA and subjected to KEGG pathway enrichment analysis. Cell proliferation was evaluated by CCK-8 and EdU incorporation assays. Proliferating cell nuclear antigen (PCNA) expression and the changes of the AMP activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway were measured by western blot analysis. Totally 4 overlapping DEGs were identified and all reduced in BC samples. ABCA8 with high diagnostic and prognostic values was selected for further exploration. Low ABCA8 expression was correlated with clinicopathological features in BC patients. ABCA8 overexpression inhibited BC cell proliferation. The top 20 co-expressed genes of ABCA8 were identified by GEPIA and significantly enriched in AMPK signaling pathway. Inhibition of AMPK/mTOR pathway reversed the suppressive effect of ABCA8 on BC cell growth. These results suggested that ABCA8 overexpression repressed BC cell proliferation through regulating the AMPK/mTOR signaling pathway.