Hsa_circFOXP1 Contributes to Breast Cancer Progression through Regulating miR-338-3p

Abstract

Background: Most patients with advanced-stage breast cancer present with bone metastasis, which seriously affects their quality of life and prognosis. We aimed to investigate the potential role of and the mechanism of circular Forkhead box protein P1 (FOXP1) (hsa_circ_0008234) in bone metastasis of breast cancer. Methods: The Gene Expression Omnibus database (GEO) database (GSE111504) was used to screen the differentially expressed circular RNAs (circRNAs) in metastatic breast cancer. The related expression of circular FOXP1 (circFOXP1) and miRNA was measured by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Cellular experiments were performed to assess the influence of circFOXP1 in breast cancer cells. After co-culture of circFOXP1 siRNA-transfected MDA-MB-231 cells and bone marrow-derived mesenchymal stem cells (BMSCs), the effect of circFOXP1 on osteogenic genes was detected. Bioinformatic Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using clusterProfilter 4.8.2 and R package version 4.3. Results: circFOXP1 was upregulated in patients with breast cancer, particularly in bone metastasis breast cancer. Silencing of circFOXP1 decreased the abilities of proliferation, migration, and invasion. The increased alkaline phosphatase (ALP) activity and osteogenic gene expression of BMSCs co-cultured with the MDA-MB-231/si-circRNA group was observed. miR-338-3p was a target miRNA of circFOXP1. Bioinformatic enrichment analysis indicated that the targeted mRNAs were involved in in MAPK pathway, regulation of actin cytoskeleton, tight junction, Ras pathway, and PI3K-AKT pathway. Conclusions: circFOXP1 upregulation was related to bone metastasis of breast cancer. Silencing of circFOXP1 in breast cancer cells might repress breast cancer cellular activities and facilitate osteogenetic differentiation of BMSCs in the microenvironment by targeting miR-338-3p. circFOXP1 might be a therapeutic target for patients with bone metastasis of breast cancer.