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Identification and Validation of UPF1 as a Novel Prognostic Biomarker in Renal Clear Cell Carcinoma

Background: Up frameshift protein 1 (UPF1) is a key component of nonsense-mediated mRNA decay (NMD) of mRNA containing premature termination codons (PTCs). The dysregulation of UPF1 has been reported in various cancers. However, the expression profile of UPF1 and its clinical significance in clear c...

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Autores principales: Wu, Chun, Li, Hongmu, Chang, Wuguang, Zhong, Leqi, Zhang, Lin, Wen, Zhesheng, Mai, Shijuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9690017/
https://www.ncbi.nlm.nih.gov/pubmed/36421841
http://dx.doi.org/10.3390/genes13112166
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author Wu, Chun
Li, Hongmu
Chang, Wuguang
Zhong, Leqi
Zhang, Lin
Wen, Zhesheng
Mai, Shijuan
author_facet Wu, Chun
Li, Hongmu
Chang, Wuguang
Zhong, Leqi
Zhang, Lin
Wen, Zhesheng
Mai, Shijuan
author_sort Wu, Chun
collection PubMed
description Background: Up frameshift protein 1 (UPF1) is a key component of nonsense-mediated mRNA decay (NMD) of mRNA containing premature termination codons (PTCs). The dysregulation of UPF1 has been reported in various cancers. However, the expression profile of UPF1 and its clinical significance in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods: In order to detect UPF1 expression in ccRCC and its relationship with the clinical features of ccRCC, bulk RNA sequencing data were analyzed from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and ArrayExpress databases. The impact of UPF1 on the immune microenvironment of ccRCC was evaluated by multiple immune scoring algorithms to identify the cell groups that typically express UPF1 using ccRCC single cell sequencing (scRNA) data. In addition, genes co-expressed with UPF1 were identified by the weighted gene correlation network analysis (WGCNA), followed by KEGG and Reactome enrichment analysis. A series of functional experiments were performed to assess the roles of UPF1 in renal cancer cells. Finally, pan-cancer analysis of UPF1 was also performed. Results: Compared with normal tissues, the expression levels of UPF1 mRNA and protein in tumor tissues of ccRCC patients decreased significantly. In addition, patients with low expression of UPF1 had a worse prognosis. Analysis of the immune microenvironment indicated that UPF1 immune cell infiltration was closely related and the ccRCC scRNA-seq data identified that UPF1 was mainly expressed in macrophages. WGCNA analysis suggested that the functions of co-expressed genes are mainly enriched in cell proliferation and cellular processes. Experimental tests showed that knockdown of UPF1 can promote the invasion, migration and proliferation of ccRCC cells. Lastly, pan-cancer analysis revealed that UPF1 disorders were closely associated with various cancer outcomes. Conclusions: UPF1 may play a tumor suppressive role in ccRCC and modulate the immune microenvironment. The loss of UPF1 can predict the prognosis of ccRCC, making it a promising biomarker and providing a new reference for prevention and treatment.
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spelling pubmed-96900172022-11-25 Identification and Validation of UPF1 as a Novel Prognostic Biomarker in Renal Clear Cell Carcinoma Wu, Chun Li, Hongmu Chang, Wuguang Zhong, Leqi Zhang, Lin Wen, Zhesheng Mai, Shijuan Genes (Basel) Article Background: Up frameshift protein 1 (UPF1) is a key component of nonsense-mediated mRNA decay (NMD) of mRNA containing premature termination codons (PTCs). The dysregulation of UPF1 has been reported in various cancers. However, the expression profile of UPF1 and its clinical significance in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods: In order to detect UPF1 expression in ccRCC and its relationship with the clinical features of ccRCC, bulk RNA sequencing data were analyzed from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and ArrayExpress databases. The impact of UPF1 on the immune microenvironment of ccRCC was evaluated by multiple immune scoring algorithms to identify the cell groups that typically express UPF1 using ccRCC single cell sequencing (scRNA) data. In addition, genes co-expressed with UPF1 were identified by the weighted gene correlation network analysis (WGCNA), followed by KEGG and Reactome enrichment analysis. A series of functional experiments were performed to assess the roles of UPF1 in renal cancer cells. Finally, pan-cancer analysis of UPF1 was also performed. Results: Compared with normal tissues, the expression levels of UPF1 mRNA and protein in tumor tissues of ccRCC patients decreased significantly. In addition, patients with low expression of UPF1 had a worse prognosis. Analysis of the immune microenvironment indicated that UPF1 immune cell infiltration was closely related and the ccRCC scRNA-seq data identified that UPF1 was mainly expressed in macrophages. WGCNA analysis suggested that the functions of co-expressed genes are mainly enriched in cell proliferation and cellular processes. Experimental tests showed that knockdown of UPF1 can promote the invasion, migration and proliferation of ccRCC cells. Lastly, pan-cancer analysis revealed that UPF1 disorders were closely associated with various cancer outcomes. Conclusions: UPF1 may play a tumor suppressive role in ccRCC and modulate the immune microenvironment. The loss of UPF1 can predict the prognosis of ccRCC, making it a promising biomarker and providing a new reference for prevention and treatment. MDPI 2022-11-20 /pmc/articles/PMC9690017/ /pubmed/36421841 http://dx.doi.org/10.3390/genes13112166 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Chun
Li, Hongmu
Chang, Wuguang
Zhong, Leqi
Zhang, Lin
Wen, Zhesheng
Mai, Shijuan
Identification and Validation of UPF1 as a Novel Prognostic Biomarker in Renal Clear Cell Carcinoma
title Identification and Validation of UPF1 as a Novel Prognostic Biomarker in Renal Clear Cell Carcinoma
title_full Identification and Validation of UPF1 as a Novel Prognostic Biomarker in Renal Clear Cell Carcinoma
title_fullStr Identification and Validation of UPF1 as a Novel Prognostic Biomarker in Renal Clear Cell Carcinoma
title_full_unstemmed Identification and Validation of UPF1 as a Novel Prognostic Biomarker in Renal Clear Cell Carcinoma
title_short Identification and Validation of UPF1 as a Novel Prognostic Biomarker in Renal Clear Cell Carcinoma
title_sort identification and validation of upf1 as a novel prognostic biomarker in renal clear cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9690017/
https://www.ncbi.nlm.nih.gov/pubmed/36421841
http://dx.doi.org/10.3390/genes13112166
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