title: Cyclic AMP responsive element-binding protein promotes renal cell carcinoma proliferation probably via the expression of spindle and kinetochore-associated protein 2.
abstract: 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.
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China.|Laboratory of Kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, China.
authors.forename: Haihui
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China.|Laboratory of Kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Pathology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310031, China.
authors.forename: Yanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Urologic Surgery, Ningbo Urology and Nephrology Hospital, Ningbo 315000, China.|Laboratory of Kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urologic Surgery, Ningbo Urology and Nephrology Hospital, Ningbo 315000, China.|Laboratory of Kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, China.
authors.forename: Shuaishuai
authors.initials: S
authors.lastname: Huang
authors.affiliation: Ningbo Medical Center, LiHuiLi Hospital, Medical School, Ningbo University, Ningbo 315041, China.
authors.forename: Kaitai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China.|Laboratory of Kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, China.
authors.forename: Michael
authors.initials: M
authors.lastname: Hehir
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fang
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China.
authors.forename: Jeff X
authors.initials: JX
authors.lastname: Zhou
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China.|Laboratory of Kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Urologic Surgery, Ningbo Urology and Nephrology Hospital, Ningbo 315000, China.|Laboratory of Kidney Carcinoma, Ningbo Urology and Nephrology Hospital, Urology and Nephrology Institute of Ningbo University, Ningbo 315000, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ren
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005260:Female; D064593:Heterografts; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged
chemical_list: C115163:CREB1 protein, human; D002868:Chromosomal Proteins, Non-Histone; D017362:Cyclic AMP Response Element-Binding Protein; C516428:SKA2 protein, human
keywords: CREB; RCC; SKA2; proliferation
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