Long non-coding RNA FOXD2-AS1/miR-150-5p/PFN2 axis regulates breast cancer malignancy and tumorigenesis

Breast cancer (BC) is a common cancer and leading cause of cancer-associated mortality in women. Abnormal expression of long non-coding RNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) was associated with the development of a number of tumors. However, whether FOXD2-AS1 is dysregulated in BC and its underlying mechanisms remain unclear. In the present study, it was identified that FOXD2-AS1 expression was upregulated in BC tissue, cell lines and sphere subpopulation. Additionally, the abnormal upregulation of FOXD2-AS1 predicted poor prognosis in patients with BC. Furthermore, downregulation of FOXD2-AS1 decreased cell proliferation, and migratory and invasive abilities in BC cells, and decreased the growth of transplanted tumors in vivo. Downregulation of FOXD2-AS1 decreased the percentage of CD44 antigen(+)/signal transducer CD24(-) in breast cancer stem cell (BCSC) cells, and decreased the expression of numerous stem factors, including Nanog, octamer-binding transcription factor 4 (Oct4), and sex determining region Y-box 2 (SOX2), and inhibited the epithelial-mesenchymal transition process. FOXD2-AS1 was identified to be primarily located in the cytoplasm. Using bioinformatics analysis, a reporter gene assay and reverse transcription-polymerase chain reaction assays, it was demonstrated that microRNA (miR)-150-5p was able to bind directly with the 3-untranslated region of FOXD2-AS1 and PFN2 mRNA. miR-150-5p mimics decreased the cell proliferation, migration and invasion of BC cells. FOXD2-AS1 knockdown significantly inhibited the miR-150-5p inhibitor-induced increase in Nanog, Oct4 and SOX2 expression. The miR-150-5p inhibitor-induced increase in N-cadherin, and decrease in E-cadherin and vimentin was inhibited by FOXD2-AS1 knockdown. Profilin 2 (PFN2) expression was significantly upregulated in BC tissues. Additionally, the abnormal upregulation of PFN2 was associated with poor prognosis in patients with BC. FOXD2-AS1 and PFN2 expression was positively correlated. Collectively, the present results demonstrated the role of the FOXD2-AS1/miR-150-5p/PFN2 axis in the development of BC, and provides novel targets for the treatment of BC, and potential biomarkers for diagnosis and prognosis of BC.