Characterization of tumor suppressor CYLD expression in clear cell renal cell carcinoma

Cyld is a tumor suppressor gene that has attracted particular interest recently, due to its involvement in many types of neoplasia, including head and neck squamous cell carcinoma, multiple myeloma, melanoma, hepatocellular carcinoma and colon cancer. Cyld encodes a predominantly cytoplasmic protein (CYLD), which is a deubiquitinating enzyme that regulates primarily cell survival and cell division pathways. Studies on the molecular function of CYLD have shown that it can modulate NF-kappa B, JNK, p38, TGF-beta, Wnt and Notch signaling. The present study aimed to investigate whether CYLD expression can be correlated with the development of clear cell renal cell carcinoma (ccRCC).Towards this goal, immunohistochemistry and Real Time KR experiments were performed in order to analyze CYLD expression in clear cell renal cell carcinoma and matched normal tissue specimens. In addition, a clonogenic assay was performed to analyze the effect of CYLD wt and a catalytically inactive mutant CYLD on the growth of human embryonic kidney cells. The results of the present study show that CYLD is downregulated at protein and mRNA level in patients with ccRCC.This is further corroborated by the results of a clonogenic assay, which showed a deubiquitinating activity-dependent growth inhibitory role of CYLD in human embryonic kidney cells. Our results support the notion that CYLD can have a tumor suppressing role, at least in a subset of clear cell renal cell carcinoma, suggesting that it can be incorporated in the future in the development of targeted therapeutic approaches.