Emerging evidence shows that the aberrantly expressed cyclic AMP responsive element-binding protein (CREB) is associated with tumor development and progression in several cancers. Spindle and kinetochore-associated protein 2 (SKA2) is essential for regulating the progress of mitosis. In this study, we evaluate in vitro and in vivo the functional relationship between CREB and SKA2 in renal cell carcinoma (RCC). Suppressing and replenishing CREB levels were used to manipulate SKA2 expression, observing the effects on RCC cell lines. Computational prediction and ChIP assay identified that CREB targeted ska2 by binding its CRE sequence in the human genome. Overexpression of CREB reversed the inhibited cell growth following siSKA2 treatment, and reduced the number of cells holding in mitosis. Decreased expression of CREB suppressed RCC cell growth and xenograft tumor formation, accompanied by reduced expression of SKA2. In RCC tumor samples from patients, mRNA for SKA2 were plotted near those of CREB in each sample, with significantly increased immunohistochemical staining of higher SKA2 and CREB in the higher TNM stages. The study adds evidence that CREB, a tumor oncogene, promotes RCC proliferation. It probably achieves this by increasing SKA2 expression.

Spindle and kinetochore-associated 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 transcription-quantitative 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 epithelial-mesenchymal transition proteins, including fibronectin, N-cadherin and vimentin, whereas there were no alterations in the protein expression levels of E-cadherin. Conversely, upregulation of SKA2 decreased the expression levels of E-cadherin, and increased N-cadherin, fibronectin and vimentin levels. Notably, it was demonstrated that E-cadherin was translocated from the cytoplasm to the nucleus in siSKA2-transfected 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 E-cadherin from the cytoplasm to the nucleus. SKA2 mediates invasion and metastasis in human breast cancer via EMT

Objectives. To identify the 20 most important and most preventable health problems that should be addressed in the next 20 years in China. Methods. In 2015, we applied a modified electronic Delphi technique to reach consensus from a panel of top Chinese health experts (n = 70), who were requested to identify 20 health problems that, in their judgment, were most important and preventable. We also compared the results with evidences from epidemiological studies on disease-specific mortalities and disability-adjusted life years. Results. Consensus was reached after the second-round survey. The final agreed-upon 20 most important and most preventable health problems included 9 noncommunicable diseases, 4 communicable diseases, 2 unhealthy behaviors, and 2 forms of environmental pollution, plus depression, road injury, and contamination of food with pesticides, antibiotics, and hormone residues. The results are supported by relevant epidemiological studies in China. Conclusions. The 20 most important and most preventable health problems in China for the next 20 years, agreed upon by a panel of top Chinese health experts, should be taken into consideration in national policymaking.