miR-223-3p targets FBXW7 to promote epithelial-mesenchymal transition and metastasis in breast cancer

Abstract

Background: Breast cancer is the most common malignant tumor diagnosed in women. It is the second leading cause of cancer-related death among women in the world. Aberrant expression of microRNAs (miRNAs) have been identified to be involved in the development and progression of breast cancer. The aim of this study was to investigate the function of miR-223-3p in breast cancer progression and metastasis. Methods: qRT-PCR was used to analyze the expression levels of miR-223-3p in breast cancer tissues and cell lines. Wound healing and Matrigel assays were used to examine cell motility and invasiveness. FBXW7 3′-UTR construct and luciferase reporter assays were performed for the target gene. Results: miR-223-3p was overexpressed in breast cancer tissue and cell lines. A high level of miR-223-3p was associated with poor prognosis in breast cancer patients. In addition, overexpressed miR-223-3p promoted the migration and invasion of breast cancer cells in vitro and in vivo. Mechanistically, we found that tumor suppressor gene FBXW7 is a target of miR-223-3p. Luciferase activity reporter assay indicated miR-223-3p could directly bind with the 3′-UTR of FBXW7. miR-223-3p exhibited its oncogenic role partly by decreasing FBXW7 expression, and consequently promoted the invasion and metastasis of breast cancer cells. Conclusions: Our study revealed a physical and functional relationship among miR-223-3p and FBXW7. By negatively regulating FBXW7 expression, miR-223-3p exerts a tumor promotion role promoting cell invasion and metastasis in breast cancer.