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Pan-Cancer Analyses Reveal Oncogenic Role and Prognostic Value of F-Box Only Protein 22
The F-box protein 22 (FBXO22), an F-box E3 ligase, has been identified to be critically involved in carcinogenesis. However, a systematic assessment of the role of FBXO22 across human cancers is lacking. Here, we performed a pan-cancer analysis to explore the role of FBXO22 in 33 cancer types using...
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/PMC8818750/ https://www.ncbi.nlm.nih.gov/pubmed/35141150 http://dx.doi.org/10.3389/fonc.2021.790912 |
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author | Chen, Sen Ma, Shuangxin Yan, Jiaoyan Wang, Haiqing Ding, Bojiao Guo, Zihu Ma, Yaohua Chen, Xuetong Wang, Yonghua |
author_facet | Chen, Sen Ma, Shuangxin Yan, Jiaoyan Wang, Haiqing Ding, Bojiao Guo, Zihu Ma, Yaohua Chen, Xuetong Wang, Yonghua |
author_sort | Chen, Sen |
collection | PubMed |
description | The F-box protein 22 (FBXO22), an F-box E3 ligase, has been identified to be critically involved in carcinogenesis. However, a systematic assessment of the role of FBXO22 across human cancers is lacking. Here, we performed a pan-cancer analysis to explore the role of FBXO22 in 33 cancer types using multiomic data from The Cancer Genome Atlas (TCGA). First, we found that high FBXO22 expression in multiple cancers was closely associated with poor overall survival and relapse-free survival. Next, we identified ten proteins that interact with FBXO22 and 13 of its target substrates using the STRING database and a literature search to explore the regulatory role of FBXO22 in tumorigenesis. Genes encoding these proteins were found to be significantly enriched in cell cycle negative regulation and ubiquitination pathways. This was confirmed in nonsmall cell lung cancer A549 cells, where FBXO22 overexpression enhanced cyclin-dependent kinase 4 (CDK4) protein levels and promoted cell proliferation. Similarly, overexpression or interference of FBXO22 changed the protein level of one of its substrates, PTEN. Additionally, we found that FBXO22 mutations were accompanied by altered substrate expression, especially in uterine corpus endometrial carcinoma and lung adenocarcinoma; endometrial carcinoma patients with FBXO22 genetic alterations also had better overall and relapse-free survival. Notably, FBXO22 methylation levels were also decreased in most tumors, and hypomethylation of FBXO22 was associated with poor overall survival, relapse-free interval, and progression-free interval in pancreatic adenocarcinoma. Finally, we analyzed the correlation between the abundance of tumor infiltrating lymphocytes (TILs) and FBXO22 expression, copy number variation, and methylation. Multiple algorithms revealed that high FBXO22 expression was associated with lower TIL levels, especially in lung adenocarcinoma, lung squamous cell carcinoma, and sarcoma. Taken together, our findings demonstrate that FBXO22 degrades tumor suppressor genes by ubiquitination and inhibits the cell cycle to promote nonsmall cell lung cancer progression. Our study also provides a relatively comprehensive understanding of the oncogenic role of FBXO22 in different tumors. |
format | Online Article Text |
id | pubmed-8818750 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88187502022-02-08 Pan-Cancer Analyses Reveal Oncogenic Role and Prognostic Value of F-Box Only Protein 22 Chen, Sen Ma, Shuangxin Yan, Jiaoyan Wang, Haiqing Ding, Bojiao Guo, Zihu Ma, Yaohua Chen, Xuetong Wang, Yonghua Front Oncol Oncology The F-box protein 22 (FBXO22), an F-box E3 ligase, has been identified to be critically involved in carcinogenesis. However, a systematic assessment of the role of FBXO22 across human cancers is lacking. Here, we performed a pan-cancer analysis to explore the role of FBXO22 in 33 cancer types using multiomic data from The Cancer Genome Atlas (TCGA). First, we found that high FBXO22 expression in multiple cancers was closely associated with poor overall survival and relapse-free survival. Next, we identified ten proteins that interact with FBXO22 and 13 of its target substrates using the STRING database and a literature search to explore the regulatory role of FBXO22 in tumorigenesis. Genes encoding these proteins were found to be significantly enriched in cell cycle negative regulation and ubiquitination pathways. This was confirmed in nonsmall cell lung cancer A549 cells, where FBXO22 overexpression enhanced cyclin-dependent kinase 4 (CDK4) protein levels and promoted cell proliferation. Similarly, overexpression or interference of FBXO22 changed the protein level of one of its substrates, PTEN. Additionally, we found that FBXO22 mutations were accompanied by altered substrate expression, especially in uterine corpus endometrial carcinoma and lung adenocarcinoma; endometrial carcinoma patients with FBXO22 genetic alterations also had better overall and relapse-free survival. Notably, FBXO22 methylation levels were also decreased in most tumors, and hypomethylation of FBXO22 was associated with poor overall survival, relapse-free interval, and progression-free interval in pancreatic adenocarcinoma. Finally, we analyzed the correlation between the abundance of tumor infiltrating lymphocytes (TILs) and FBXO22 expression, copy number variation, and methylation. Multiple algorithms revealed that high FBXO22 expression was associated with lower TIL levels, especially in lung adenocarcinoma, lung squamous cell carcinoma, and sarcoma. Taken together, our findings demonstrate that FBXO22 degrades tumor suppressor genes by ubiquitination and inhibits the cell cycle to promote nonsmall cell lung cancer progression. Our study also provides a relatively comprehensive understanding of the oncogenic role of FBXO22 in different tumors. Frontiers Media S.A. 2022-01-24 /pmc/articles/PMC8818750/ /pubmed/35141150 http://dx.doi.org/10.3389/fonc.2021.790912 Text en Copyright © 2022 Chen, Ma, Yan, Wang, Ding, Guo, Ma, Chen and Wang 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 | Oncology Chen, Sen Ma, Shuangxin Yan, Jiaoyan Wang, Haiqing Ding, Bojiao Guo, Zihu Ma, Yaohua Chen, Xuetong Wang, Yonghua Pan-Cancer Analyses Reveal Oncogenic Role and Prognostic Value of F-Box Only Protein 22 |
title | Pan-Cancer Analyses Reveal Oncogenic Role and Prognostic Value of F-Box Only Protein 22 |
title_full | Pan-Cancer Analyses Reveal Oncogenic Role and Prognostic Value of F-Box Only Protein 22 |
title_fullStr | Pan-Cancer Analyses Reveal Oncogenic Role and Prognostic Value of F-Box Only Protein 22 |
title_full_unstemmed | Pan-Cancer Analyses Reveal Oncogenic Role and Prognostic Value of F-Box Only Protein 22 |
title_short | Pan-Cancer Analyses Reveal Oncogenic Role and Prognostic Value of F-Box Only Protein 22 |
title_sort | pan-cancer analyses reveal oncogenic role and prognostic value of f-box only protein 22 |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818750/ https://www.ncbi.nlm.nih.gov/pubmed/35141150 http://dx.doi.org/10.3389/fonc.2021.790912 |
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