NPM1 is a Novel Therapeutic Target and Prognostic Biomarker for Ewing Sarcoma
Ewing sarcoma (ES) is a cancer that may originate from stem mesenchymal or neural crest cells and is highly prevalent in children and adolescents. In recent years, targeted therapies against immune-related genes have shown good efficacy in a variety of cancers. However, effective targets for immunot...
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| Published in | Frontiers in genetics Vol. 12; p. 771253 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
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26.11.2021
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| Abstract | Ewing sarcoma (ES) is a cancer that may originate from stem mesenchymal or neural crest cells and is highly prevalent in children and adolescents. In recent years, targeted therapies against immune-related genes have shown good efficacy in a variety of cancers. However, effective targets for immunotherapy in ES are yet to be developed. In our study, we first identified the immune-associated differential hub gene NPM1 by bioinformatics methods as a differentially expressed gene, and then validated it using real time-PCR and western blotting, and found that this gene is not only closely related to the immune infiltration in ES, but also can affect the proliferation and apoptosis of ES cells, and is closely related to the survival of patients. The results of our bioinformatic analysis showed that NPM1 can be a hub gene in ES and an immunotherapeutic target to reactivate immune infiltration in patients with ES. In addition, treatment with NPM1 promoted apoptosis and inhibited the proliferation of ES cells. The NPM1 inhibitor NSC348884 can induce apoptosis of ES cells in a dose-dependent manner and is expected to be a potential therapeutic agent for ES. |
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| AbstractList | Ewing sarcoma (ES) is a cancer that may originate from stem mesenchymal or neural crest cells and is highly prevalent in children and adolescents. In recent years, targeted therapies against immune-related genes have shown good efficacy in a variety of cancers. However, effective targets for immunotherapy in ES are yet to be developed. In our study, we first identified the immune-associated differential hub gene NPM1 by bioinformatics methods as a differentially expressed gene, and then validated it using real time-PCR and western blotting, and found that this gene is not only closely related to the immune infiltration in ES, but also can affect the proliferation and apoptosis of ES cells, and is closely related to the survival of patients. The results of our bioinformatic analysis showed that NPM1 can be a hub gene in ES and an immunotherapeutic target to reactivate immune infiltration in patients with ES. In addition, treatment with NPM1 promoted apoptosis and inhibited the proliferation of ES cells. The NPM1 inhibitor NSC348884 can induce apoptosis of ES cells in a dose-dependent manner and is expected to be a potential therapeutic agent for ES. |
| Author | Xu, Bin Fang, Yuan Zhou, Junjie Wu, Shusheng Liu, Yulian Zhou, Yangfan |
| AuthorAffiliation | 2 The First Affiliated Hospital of (University of Science and Technology of China) USTC, Hefei , China 1 The First Affiliated Hospital of Anhui Medical University, Hefei , China |
| AuthorAffiliation_xml | – name: 1 The First Affiliated Hospital of Anhui Medical University, Hefei , China – name: 2 The First Affiliated Hospital of (University of Science and Technology of China) USTC, Hefei , China |
| Author_xml | – sequence: 1 givenname: Yangfan surname: Zhou fullname: Zhou, Yangfan organization: The First Affiliated Hospital of Anhui Medical University, Hefei, China – sequence: 2 givenname: Yuan surname: Fang fullname: Fang, Yuan organization: The First Affiliated Hospital of Anhui Medical University, Hefei, China – sequence: 3 givenname: Junjie surname: Zhou fullname: Zhou, Junjie organization: The First Affiliated Hospital of Anhui Medical University, Hefei, China – sequence: 4 givenname: Yulian surname: Liu fullname: Liu, Yulian organization: The First Affiliated Hospital of Anhui Medical University, Hefei, China – sequence: 5 givenname: Shusheng surname: Wu fullname: Wu, Shusheng organization: The First Affiliated Hospital of (University of Science and Technology of China) USTC, Hefei, China – sequence: 6 givenname: Bin surname: Xu fullname: Xu, Bin organization: The First Affiliated Hospital of Anhui Medical University, Hefei, China |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34899858$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1016/j.acthis.2015.08.006 10.3389/fimmu.2021.724741 10.1136/jitc-2020-000653 10.5402/2011/168712 10.1111/resp.12789 10.3892/etm.2019.7925 10.1016/j.trecan.2018.04.001 10.1186/1423-0127-19-53 10.1158/2326-6066.Cir-20-0949 10.1002/pbc.24429 10.1126/science.aav7062 10.1200/jco.2014.59.5256 10.1038/s41467-018-07767-w 10.2147/ott.S258439 10.1158/0008-5472.Can-18-2403 10.1186/1471-2105-9-559 10.1038/leu.2017.30 10.1159/000487143 10.2147/ott.S105862 10.1016/j.prp.2015.05.010 10.1002/cncy.22239 10.1186/1471-2105-14-7 10.3892/ijo.2017.4155 10.1186/s13046-019-1259-z 10.1038/ni.2703 10.1038/sj.onc.1205708 10.1002/jcp.30406 10.7150/thno.52717 10.1038/s41467-020-15364-z 10.1038/onc.2008.54 10.1158/1078-0432.Ccr-20-2166 10.1158/1078-0432.Ccr-14-2744 10.1038/ng.1085 10.2147/cmar.S191176 10.3389/fgene.2021.669549 10.1111/cup.13695 10.1038/ncomms3612 10.1016/j.omtn.2020.06.001 |
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| Keywords | ESC348884 Ewing sarcoma NPM1 tumor microenvironment immunotherapy |
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| License | Copyright © 2021 Zhou, Fang, Zhou, Liu, Wu and Xu. 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. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Zheng Jin Tu, Cleveland Clinic, United States These authors have contributed equally to this work This article was submitted to Human and Medical Genomics, a section of the journal Frontiers in Genetics Yingming Sun, Fujian Medical University, China Chengdong Liu, Southern Medical University, China Reviewed by: Sufang Qiu, Fujian Provincial Cancer Hospital, China |
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| Title | NPM1 is a Novel Therapeutic Target and Prognostic Biomarker for Ewing Sarcoma |
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