miR-27a promotes human breast cancer cell migration by inducing EMT in a FBXW7-dependent manner

Increasingly, evidence has revealed that aberrant microRNA (miRNA) expression is involved in breast cancer carcinogenesis and further progression, including metastasis. miRNA (miR)-27a was previously identified to be abnormally expressed and to serve pro-oncogenic functions in multiple human cancer types, including breast cancer. However, its functions and underlying mechanisms in breast cancer remain poorly understood. In the present study, it was demonstrated that miR-27a was significantly upregulated in breast cancer tissues and cell lines compared with their normal counterparts. Overexpression of miR-27a resulted in enhanced cell migration by inducing epithelial-to-mesenchymal transition, while its knockdown effectively reversed these cellular events. The present study additionally confirmed for the first time, to the best of our knowledge, that F-box and WD repeat domain containing 7 (FBXW7) is a downstream target gene of miR-27a in human breast cancer cells. FBXW7 is underexpressed in breast cancer tissues and cell lines, and is an independent positive factor for the overall survival rate of patients with breast cancer. Notably, the ectopic expression of FBXW7 may effectively suppress the epithelial-to-mesenchymal transition and migratory activity of breast cancer cells, in addition to reversing the cell migration mediated by miR-27a. Altogether, the results of the present study indicated the important function of miR-27a in regulating the metastasis of breast cancer in a FBXW7-dependent manner, and provide evidence for the potential application of miR-27a in breast cancer therapy.