SKA2 mediates invasion and metastasis in human breast cancer via EMT.

Spindle and kinetochore­associated protein 2 (SKA2) is essential for regulating the progression of mitosis. In recent years, SKA2 upregulation has been detected in various human malignancies and the role of SKA2 in tumorigenesis has received increasing attention. However, the expression and functional significance of SKA2 in breast cancer are not completely understood. To study the effects of SKA2 on breast cancer, the expression levels of SKA2 in breast cancer tissues and cell lines were evaluated by western blotting, reverse transcription­quantitative polymerase chain reaction and immunohistochemical staining. The results demonstrated that SKA2 expression was increased in breast cancer tissues and cells, and SKA2 overexpression was associated with clinical stage and lymph node metastasis. Functional investigations revealed that SKA2 knockdown in breast cancer cells significantly reduced migration and invasion, and resulted in the decreased expression levels of matrix metalloproteinase (MMP)2 and MMP9. Furthermore, the typical microtubule arrangement was altered in SKA2 small interfering RNA (siSKA2)­transfected cells. Reduced levels of SKA2 also downregulated the expression of epithelial­mesenchymal transition proteins, including fibronectin, N­cadherin and vimentin, whereas there were no alterations in the protein expression levels of E­cadherin. Conversely, upregulation of SKA2 decreased the expression levels of E­cadherin, and increased N­cadherin, fibronectin and vimentin levels. Notably, it was demonstrated that E­cadherin was translocated from the cytoplasm to the nucleus in siSKA2­transfected cells. These results demonstrated that SKA2 may be associated with breast cancer metastasis, and siSKA2 inhibited the invasion and metastasis of breast cancer via translocation of E­cadherin from the cytoplasm to the nucleus.

MiR-520d-3p antitumor activity in human breast cancer via post-transcriptional regulation of spindle and kinetochore associated 2 expression.

MicroRNAs (miRNAs) play an important role in human tumorigenesis as oncogenes or tumor suppressors by directly binding to the 3'-untranslated region of their target mRNAs. MiR-520d-3p has been reported as a tumor suppressor gene in ovarian cancer and gastric cancer, while the function of miR-520d-3p in human breast cancers is still uninvolved. In this study, we initially identified that the expression of miR-520d-3p was significantly reduced in breast cancer specimens and cell lines. The restoration of miR-520d-3p expression not only reduced breast cancer cell viability by causing the accumulation of G2 phase and cell apoptosis, but also inhibited tumorigenicity in vivo. In addition, as a critical target of miR-520d-3p, the activity of spindle and kinetochore associated 2 (SKA2) was greatly inhibited by miR-520d-3p, and overexpression of miR-520d-3p decreased the expression of SKA2. SKA2 downregulation suppressed cell viability, whereas restoration of SKA2 expression significantly reversed the inhibitory effects of miR-520d-3p antitumor activity. Furthermore, SKA2 was frequently overexpressed in clinical specimens and cell lines, and the expression levels were statistically inversely correlated with miR-520d-3p expression. In conclusion, our data demonstrated that miR-520d-3p antitumor activity is achieved by targeting the SKA2 in human breast cancer cells, suggesting that miR-520d-3p may be a potential target molecule for the therapy.