Abstract
Ubiquitin-specific protease 5 (USP5) is a deubiquitinating enzyme that functions as an oncoprotein in a variety of human cancers. However, the expression and role of USP5 in the metastasis of non-small cell lung cancer (NSCLC) have not been addressed. In this study, we examined the expression and prognostic significance of USP5 in NSCLC. The results revealed that USP5 was overexpressed and correlated with metastasis and overall survival in NSCLC tissues. A further in vitro study revealed that the levels of USP5 protein in NSCLC cells were associated with epithelial–mesenchymal transition (EMT) markers. Furthermore, USP5 overexpression significantly enhanced, whereas USP5 silencing significantly decreased the expression of EMT proteins and migration and invasion of NSCLC cells. In addition, the results from western blotting demonstrated that USP5 regulated EMT via the Wnt/β-catenin signaling pathway. Further immunohistochemical analysis revealed that USP5 was significantly associated with the expression of β-catenin and EMT markers in NSCLC tissues. Overall, USP5 upregulation is associated with tumor metastasis and poor prognosis in patients with NSCLC. USP5 promotes EMT and the invasion and migration of NSCLC cells. Therefore, USP5 may serve as a novel prognostic biomarker and provide a potential target for the treatment of metastasis in NSCLC.
Highlights
Lung cancer is the most commonly diagnosed malignancy and a prime leading cause of cancer deaths worldwide (Bray et al, 2018)
We previously reported that ubiquitin C-terminal hydrolase L1 (UCHL1), a member of deubiquitinating enzymes (DUBs), is associated with favorable prognosis in neuroblastoma (Gu et al, 2018a) and is critical for the survival and immunosuppressive function of tumor-associated immune cells (Gu et al, 2018b), suggesting that these DUBs are closely related with tumor development and progression
Adjacent normal tissues revealed weak or partly moderate Ubiquitin-specific protease 5 (USP5) staining restricted to the basal layers, whereas USP5 staining in non-small cell lung cancer (NSCLC) tissues was considerably stronger (Figure 1B)
Summary
Lung cancer is the most commonly diagnosed malignancy and a prime leading cause of cancer deaths worldwide (Bray et al, 2018). Despite advances in the treatment of NSCLC, distant metastasis remains the main factor. USP5 Promotes Tumor Metastasis contributing to disease-associated death (Chaffer and Weinberg, 2011). It is well known that EMT plays important roles in a variety of biological processes, for instance, wound healing, embryonic development, fibrosis, and organ formation (Sung et al, 2016). Recent cancer studies have revealed that EMT, which is essential for the transformation of early-stage tumors into aggressive malignancies, is an early event in tumor metastasis (Kang and Massague, 2004). Numerous studies have shown that signaling pathways such as phosphatidylinositol-3-kinase/AKT, nuclear factor-kB, mitogen-activated protein kinase, Notch, transforming growth factor (TGF)-b, and Wnt/b-catenin, among others, play crucial roles in EMT-related invasion and metastasis (Weis and Cheresh, 2011; Katsuno et al, 2013)
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