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Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer
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. Method...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273912/ https://www.ncbi.nlm.nih.gov/pubmed/35836933 http://dx.doi.org/10.3389/fmolb.2022.886904 |
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author | Li, Kai Wang, Qian Bian, Hua Chen, Zhiguo He, Haifa Zhao, Xulin Gong, Pengju |
author_facet | Li, Kai Wang, Qian Bian, Hua Chen, Zhiguo He, Haifa Zhao, Xulin Gong, Pengju |
author_sort | Li, Kai |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9273912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92739122022-07-13 Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer Li, Kai Wang, Qian Bian, Hua Chen, Zhiguo He, Haifa Zhao, Xulin Gong, Pengju Front Mol Biosci Molecular Biosciences 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. Frontiers Media S.A. 2022-06-28 /pmc/articles/PMC9273912/ /pubmed/35836933 http://dx.doi.org/10.3389/fmolb.2022.886904 Text en Copyright © 2022 Li, Wang, Bian, Chen, He, Zhao and Gong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Li, Kai Wang, Qian Bian, Hua Chen, Zhiguo He, Haifa Zhao, Xulin Gong, Pengju Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer |
title | Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer |
title_full | Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer |
title_fullStr | Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer |
title_full_unstemmed | Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer |
title_short | Comprehensive Analysis Reveals USP45 as a Novel Putative Oncogene in Pan-Cancer |
title_sort | comprehensive analysis reveals usp45 as a novel putative oncogene in pan-cancer |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273912/ https://www.ncbi.nlm.nih.gov/pubmed/35836933 http://dx.doi.org/10.3389/fmolb.2022.886904 |
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