57650

KIAA1524

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.

The aberrant expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) indicates poor prognosis and promotes EMT and metastasis. EMT, a crucial cellular process that occurs during cancer progression and metastasis, has been reported to promote drug resistance in several previous studies. Consequently, ongoing research has been focused on exploring therapeutic options for preventing EMT to delay or reverse drug resistance. Polyphyllin I (PPI) is a natural component extracted from Paris polyphylla that displays anti-cancer properties. In the present study, we investigated whether PPI can be used in the cisplatin (DDP)-resistant human gastric cancer cell line SGC7901/DDP. The results demonstrated that PPI treatment significantly inhibited cell proliferation, invasion and EMT. TGF-beta1 is known to promote EMT-induced metastasis in numerous tumor types. PPI inhibited the invasion of TGFbeta1-induced SGC7901/DDP cells in vitro. PPI also increased the mRNA and protein expression levels of E-cadherin but decreased the expression levels of vimentin. Further examination of the mechanism revealed that the CIP2A/PP2A/Akt pathway is partially involved in this regulation of EMT-related biomarkers and invasion. Furthermore, xenograft tests also confirmed the antitumor effects of PPI in vivo. We propose that PPI could be developed as a candidate drug for treating cancer invasion and migration.CI - Copyright (c) 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.