Forkhead box P3 promotes breast cancer cell apoptosis by regulating programmed cell death 4 expression.

Abstract

Forkhead box P3 (FOXP3), an X-linked tumor suppressor gene, plays an important role in breast cancer. However, the biological functions of FOXP3 in breast cancer apoptosis remain unclear. To investigate the underlying genes and networks regulated by FOXP3 in breast cancer, RNA sequencing was performed to compare FOXP3-overexpressing MDA-MB-231 cells and control MDA-MB-231 cells. Differentially expressed genes were identified, and functional enrichment analysis comparing the two groups was performed. The differentially expressed genes were mainly enriched in phagosomes, oxytocin, serotonergic synapses and the phospholipase D signaling pathway. Furthermore, gene set enrichment analysis revealed the enrichment of a gene signature associated with apoptosis in FOXP3-overexpressing MDA-MB-231 cells compared with wild-type cells. Further analysis showed that programmed cell death 4 (PDCD4), a key molecule involved in apoptosis, was overexpressed in FOXP3-MDA-MB-231 cells. Reverse transcription-quantitative PCR and western blotting showed that FOXP3 upregulated the expression of PDCD4 in breast cancer cells. Clinical sample analysis using a public database showed that the expression level of PDCD4 was associated with breast cancer clinical stages. Overall, the present study suggested that FOXP3 can promote the apoptosis of breast cancer cells by upregulating the expression of PDCD4, thus exerting a tumor suppressive function.