Overexpression of CIP2A in clear cell renal cell carcinoma promotes cellular epithelial-mesenchymal transition and is associated with poor prognosis

Abstract

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a newly characterized oncoprotein involved in a variety of malignant tumors. However, its expression pattern and biological functions in clear cell renal cell carcinoma (ccRCC) remain unclear. In the present study, our findings demonstrated that expressions of CIP2A mRNA and protein in ccRCC tissues and cell lines were significantly higher than those in paired normal renal tissues or normal renal tubular epithelial cells (P<0.05). High CIP2A level was closely correlated with T stage (P=0.001), tumor size (P=0.009), lymph node metastasis (P=0.014), vascular invasion (P=0.018) and high Snail expression (P<0.001). Additionally, ccRCC patients with high CIP2A expression had significantly shorter overall survival (OS, P<0.001) and disease-free survival (DFS, P<0.001) when compared with patients with the low expression of CIP2A. On Cox multivariate analysis, CIP2A overexpression was an independent and significant prognostic factor for OS (P=0.010) and DFS (P=0.004). Furthermore, knockdown of the CIP2A expression significantly reduced ccRCC cell invasion, with decreased Snail and Vimentin expression, and increased E-cadherin expression. Taken together, our data identified CIP2A as a critical oncoprotein involved in cell invasion and epithelial mesenchymal transition (EMT), which could serve as a therapeutic target in ccRCC.