Background:Cancerous inhibitor of protein phosphatase 2A (CIP2A) drives cellular transformation. The objective of this study was to detect the potential effects of CIP2A in renal cell carcinomas (RCCs).Methods:A total of 107 RCC patients were involved in the study. Cancerous inhibitor of protein phosphatase 2A expression was investigated by real-time PCR and immunohistochemistry. In vitro, we examined the expression of CIP2A and c-Myc and tested the migration and invasion capability of A498 and KRC/Y cells with scratch migration assay and Matrigel invasion assay after down-regulating CIP2A expression using siRNA.Results:Cancerous inhibitor of protein phosphatase 2A was over-expressed in RCC tissues. Clear cell RCC showed an even higher-CIP2A expression level than papillary or chromophobe RCC did. The CIP2A immunostaining level was positively correlated with primary tumour stage, lymph node metastasis, distant metastasis, TNM stage and histological grade (all P<0.05). High-CIP2A expression implied poor survival for patients (P<0.05). Cancerous inhibitor of protein phosphatase 2A depletion by siRNA down-regulated c-Myc expression and attenuated the migration and invasion of RCC cells.Conclusion:Higher-CIP2A expression positively correlates with the aggressive phenotype of RCCs, and predicts poor prognosis for patients. Cancerous inhibitor of protein phosphatase 2A may be a novel target for prevention and treatment of RCC metastasis and recurrence.

Eukaryotic translation initiation factors (eIFs) constitute a new class of therapeutic cancer targets. EIF3b is the major scaffold protein of eIF3 (the largest core of eIFs). We sought to define the role played by and the mechanism of action of eIF3b in patients with clear cell renal cell carcinoma (ccRCC). We found that high-level eIF3b expression in tumors was not only associated with an aggressive tumor phenotype, but was also independently prognostic for patients with ccRCC. Knockdown of eIF3b impaired the action of the Akt pathway, thus inhibiting cell proliferation by disrupting the cell cycle and triggering apoptosis. Furthermore, the epithelial-to-mesenchymal transition was impaired after eIF3b depletion, via suppression of cell migration and invasion. Additionally, eIF3b knockdown significantly inhibited the growth of subcutaneous xenografts in mice. Together, these data show that eIF3b is both a promising prognostic biomarker and a potential therapeutic target for patients with ccRCC.

Helicobacter pylori (H. pylori) infection is the strongest risk factor for the initiation and progression of gastric cancer. However, the mechanism of H. pylori-induced pathogenesis remains unclear. In this study, we investigate the role of H. pylori infection in JMJD2B upregulation and the mechanism underlying gastric carcinogenesis. We find that JMJD2B can be induced by H. pylori infection via β-catenin pathway. β-catenin directly binds to JMJD2B promoter and stimulates JMJD2B expression following H. pylori infection. Increased JMJD2B, together with NF-κB, binds to COX-2 promoter to enhance its transcription by demethylating H3K9me3 locally. JMJD2B and COX-2 expression is upregulated in H. pylori infected mice in vivo. Furthermore, JMJD2B and COX-2 expression is gradually increased in human gastric tissues from gastritis to gastric cancer. The level of JMJD2B and COX-2 in H. pylori-positive gastritis tissues is significantly higher than that in H. pylori-negative tissues. Moreover, a positive correlation between JMJD2B and COX-2 expression is found in both gastritis and gastric cancer tissues. Therefore, JMJD2B is a crucial factor in triggering H. pylori-induced chronic inflammation and progression of gastric carcinogenesis and it may serve as a novel target for the intervention of gastric cancer.