Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer

Abstract

Background: Deubiquitinating enzymes specifically removes ubiquitin molecules from ubiquitin-tagged target proteins, thereby inhibiting the degradation of target proteins and playing an important role in tumor. However, the mechanism of deubiquitinating enzyme USP45 in tumors remains unclear.Methods: Based on the RNA-seq data of tissues and cell lines in The Cancer Genome Atlas (TCGA) database, GTEx and CCLE database, the pan-cancer analysis of USP45 expression and survival outcome were performed using R software and Kaplan-Meier Plotter. The structural variants, gene mutations and gene copy number alteration of USP45 were analyzed using the TCGA Pan-Cancer Atlas Studies dataset in the cBioPortal database. The relationships between USP45 and mRNA methylation, tumor heterogeneity, tumor stemness, and tumor immunity were performed by Sangerbox platform and TIMER2.0 using Pearson correlation analysis. Through the ENCORI database and string database, we constructed the ceRNA regulatory mechanism and protein-protein interaction network for USP45. Based on the RNA-seq data in TCGA and GTEx databases, we also constructed the downstream regulatory network for USP45 using the Limma and ClusterProfiler packages of R software. At last, the protein expression levels of USP45 were detected by immunohistochemistry in tumor tissue microarrays.Results: USP45 is upregulated in most types of tumors and negatively correlated with the overall survival and recurrence-free survival of patient. Furthermore, the structural variation, gene mutations and gene copy number variation of USP45 were identified in different types of tumors. The pan-cancer analysis showed that USP45 was closely related to mRNA methylation, tumor heterogeneity and tumor stemness. In most types of tumors, the expression of USP45 was positively correlated with many immune checkpoint molecules and immune regulators such as PD-L1, while negatively correlated with the infiltration levels of NK cells, Th1 cells, macrophages, and dendritic cells in the tumor microenvironment. Finally, we constructed the ceRNA regulatory network, protein-protein interaction network and downstream regulatory network for USP45 in different types of tumors.Conclusion: Our study firstly explored the putative oncogenic role of USP45 in pan-cancer, and provided insights for further investigation of USP45.

USP10 Contributes to Colon Carcinogenesis via mTOR/S6K Mediated HIF-1α but Not HIF-2α Protein Synthesis

“…It has been reported that several DUBs—USP7, USP10, USP33, USP40, USP45, USP46, YOD1, and JOSD1 are involved in carcinogenesis [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Moreover, studies have shown that USP7, USP10, USP33, and USP46 are all involved in the progression of colorectal cancer [ 22 , 26 , 30 , 31 , 32 , 33 ].…”

BCL2A1 is associated with tumor-associated macrophages and unfavorable prognosis in human gliomas

“…The type and number of immune cells in the tumor microenvironment are related to tumor development and immunotherapy [ 22 ]. Therefore, we utilized the TIMER 2.0 dataset to evaluate the correlation between BCL2A1 expression and immune cell infiltration levels in glioma.…”

Genetic variants in NER pathway genes predict hepatitis B virus-related hepatocellular carcinoma survival

“…Ubiquitin speci c peptidase 45 (USP45) is located on chromosome 6q16.2, encoding a deubiquitylase, which is essential for maintaining the DNA repair ability of XPF-ERCC1 [38] . It has been reported that high USP45 expression levels are associated with poor OS in HCC patients by in uencing tumor heterogeneity and tumor stemness [39] . In addition, rs41288947 of USP45 was found to be associated with an increased risk of early-onset arterial coronary disease [40] .…”