Research Papers:

Cyclic AMP responsive element-binding protein promotes renal cell carcinoma proliferation probably via the expression of spindle and kinetochore-associated protein 2

Haihui Zhuang, Xiangyu Meng, Yanyuan Li, Xue Wang, Shuaishuai Huang, Kaitai Liu, Michael Hehir, Rong Fang, Lei Jiang, Jeff X. Zhou, Ping Wang _ and Yu Ren

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Oncotarget. 2016; 7:16325-16337. https://doi.org/10.18632/oncotarget.7017

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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

Correspondence to:

Ping Wang, e-mail: pinoav@hotmail.com

Yu Ren, e-mail: nbrenyu@163.com

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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