Cyclic AMP responsive element-binding protein promotes renal cell carcinoma proliferation probably via the expression of spindle and kinetochore-associated protein 2
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Haihui Zhuang1,4, Xiangyu Meng1,4, Yanyuan Li3, Xue Wang2,4, Shuaishuai Huang2,4, Kaitai Liu5, Michael Hehir1,4, Rong Fang1, Lei Jiang1, Jeff X. Zhou1, Ping Wang1,4, Yu Ren2,4
1Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China
2Department of Urologic Surgery, Ningbo Urology and Nephrology Hospital, Ningbo 315000, China
3Department of Pathology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310031, China
4Laboratory of Kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, China
5Ningbo Medical Center, LiHuiLi Hospital, Medical School, Ningbo University, Ningbo 315041, China
Ping Wang, e-mail: email@example.com
Yu Ren, e-mail: firstname.lastname@example.org
Keywords: CREB, SKA2, RCC, proliferation
Received: May 29, 2015 Accepted: January 01, 2016 Published: January 25, 2016
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.
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