Abstract
BackgroundFOXP3, as a tumour suppressor gene, has a vital function in inhibiting the metastasis of breast cancer cells, but the mechanisms by which it inhibits metastasis have not been fully elucidated. This study intended to explore a new mechanism by which FOXP3 inhibits breast cancer metastasis.MethodsBioinformatic analysis was performed to identify potential downstream molecules of FOXP3. The function of FOXP3 in inhibiting MTA1 expression at the mRNA and protein levels was verified by real-time PCR and Western blot analysis. The interaction between FOXP3 and the MTA1 promoter was verified by transcriptomic experiments. In vitro and in vivo experiments were used to determine whether the regulation of MTA1 by FOXP3 affected the invasion and migration of breast cancer cells. Immunohistochemistry was adopted to explore the correlation between the expression levels of FOXP3 and MTA1 in breast cancer samples.ResultsBioinformatics-based sequencing suggested that MTA1 is a potential downstream molecule of FOXP3. FOXP3 downregulated the expression of MTA1 in breast cancer cells by directly inhibiting MTA1 promoter activity. Importantly, FOXP3’s regulation of MTA1 affected the ability of breast cancer cells to invade and metastasize in vitro and in vivo. Moreover, analysis of clinical specimens showed a significant negative correlation between the expression levels of FOXP3 and MTA1 in breast cancer.ConclusionWe systematically explored a new mechanism by which FOXP3 inhibits breast cancer metastasis via the FOXP3-MTA1 pathway.
Highlights
FOXP3, as a tumour suppressor gene, has a vital function in inhibiting the metastasis of breast cancer cells, but the mechanisms by which it inhibits metastasis have not been fully elucidated
We used the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to identify the signalling pathways enriched with the target genes of FOXP3, and the results showed that the target genes of FOXP3 might be involved in the regulation of cell movement and migration pathways (Figure 1A)
The differentially expressed genes identified in MCF7-vector and MCF7-FOXP3 cells were further subjected to Gene Ontology (GO) analysis to identify their participation in cellular biological processes, and the results showed that the identified differentially expressed genes participate in cell adhesion and cytoskeletal reorganization (Figure 1B)
Summary
FOXP3, as a tumour suppressor gene, has a vital function in inhibiting the metastasis of breast cancer cells, but the mechanisms by which it inhibits metastasis have not been fully elucidated. This study intended to explore a new mechanism by which FOXP3 inhibits breast cancer metastasis. An abundance of data show that the metastasis of tumour cells is an important cause of poor prognosis and death in breast cancer patients [3, 4]. A large number of studies have shown that FOXP3 is a tumour suppressor gene in breast cancer [9, 10]. FOXP3 can regulate the expression of proto-oncogenes and tumour suppressor genes to perform its anticancer function. The molecular mechanism underlying this process needs more specific and more comprehensive study
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