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Abstract
BackgroundClear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. Ubiquitin-specific protease (USP)44 has been reported to be involved in various cancers. We investigated the function, role and molecular mechanism of USP44 in ccRCC.MethodsData obtained from the Cancer Genome Atlas Data Portal and Gene Expression Omnibus database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. USP44 function in the proliferation and migration of tumor cells was assessed by cellular and molecular analyses using ccRCC lines (786-O cells and Caki-1 cells).ResultsUSP44 showed low expression in ccRCC cancer tissues compared with that in normal tissue. USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival. USP44 overexpression inhibited the proliferation and migration of 786-O cells and Caki-1 cells significantly. USP44 overexpression also prohibited cell proliferation by upregulating expression of P21, downregulating cyclin-D1 expression, and inhibiting cell migration by downregulating expression of matrix metalloproteinase (MMP)2 and MMP9. USP44 knockdown enhanced the proliferation and migration of 786-O cells and Caki-1 cells. USP44 function in inhibiting the proliferation and migration of 786-O cells and Caki-1 cells was associated with phosphorylation of Jun N-terminal kinase (JNK).ConclusionUSP44 may be a marker in predicting ccRCC progression. Inhibition by USP44 of the proliferation and migration of 786-O cells and Caki-1 cells is dependent upon the JNK pathway.
Highlights
Clear cell renal cell carcinoma is the most common form of adult kidney cancer
USP44 expression is deceased in Clear cell renal cell carcinoma (ccRCC) tissue and is correlated with the tumor stage, tumor grade
Patient survival Analyses of information from the TCGA Data Portal demonstrated that USP44 expression was significantly lower in ccRCC specimens than that in normal tissues (Fig. 1a)
Summary
Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. Ubiquitinspecific protease (USP) has been reported to be involved in various cancers. Renal cell carcinoma (RCC) is represents 80–90% of adult kidney cancers. The most efficacious treatment for early-stage clear cell renal cell carcinoma (ccRCC) is surgery and targeted therapy [2]. USP44 is a member of a family of deubiquitinating enzymes and has an important role in human cancers [8]. USP44 can stabilize the protein expression of protectin in the cycle of healthy cells until all the chromosomes match correctly with spindle fibers and prevent immature mitosis. By inhibiting USP44 expression in mice, the proportion of aneuploid cells and chromosomal instability can be increased significantly, making them more prone to malignant transformation [10, 11]. Zou and colleagues showed that USP44 overexpression promotes the malignancy of glioma [12]
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