Overexpression of USP5 contributes to tumorigenesis in non-small cell lung cancer via the stabilization of β-catenin protein.

The ubiquitin-specific protease 5 (USP5), a deubiquitinating enzyme, has been identified as a tumor promoter in several types of human cancer. However, the role of USP5 in non-small lung cancer (NSCLC) has not yet been elucidated. In this study, we found that USP5 was upregulated in NSCLC tissues compared with normal tissues. High expression of USP5 was correlated with large primary tumor size, poor differentiation and advanced TNM stage, and led to a significantly shorter overall survival (OS). USP5 overexpression enhanced, whereas USP5 silencing impaired the cell proliferation and colony formation of NSCLC cells in vitro. Moreover, knockdown of USP5 in H1299 cells inhibited tumor growth in vivo. Mechanistically, we found that USP5 deubiquitinated β-catenin, prevented ubiquitination mediated β-catenin degradation and promoted β-catenin nuclear accumulation, leading to the activation of Wnt/β-catenin signal pathway in NSCLC cells. Taken together, these findings suggest that USP5 functions as an oncogene in NSCLC and its oncogenic activity involves in part through Wnt/β-catenin signal pathway.