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IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma
The clinical features of EBV-positive diffuse large B cell lymphoma (DLBCL) indicate a poorer prognosis than EBV-negative DLBCL. Currently, there is no efficacious drug for EBV-positive DLBCL. The cytokine interleukin-21 (IL-21) has been reported to be pro-apoptotic in DLBCL cell lines and is being...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378064/ https://www.ncbi.nlm.nih.gov/pubmed/32704112 http://dx.doi.org/10.1038/s41598-020-69227-0 |
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author | Wang, Yuxuan Wang, Chengcheng Cai, Xiyunyi Mou, Chang Cui, Xueting Zhang, Yingying Ge, Feng Dong, Hao Hao, Yuanyuan Cai, Lei Wu, Shuting Feng, Chenjie Chen, Jiamin Li, Jianyong Xu, Wei Fan, Lei Xie, Weijia Tong, Yue Gu, Harvest Feng Wu, Liang |
author_facet | Wang, Yuxuan Wang, Chengcheng Cai, Xiyunyi Mou, Chang Cui, Xueting Zhang, Yingying Ge, Feng Dong, Hao Hao, Yuanyuan Cai, Lei Wu, Shuting Feng, Chenjie Chen, Jiamin Li, Jianyong Xu, Wei Fan, Lei Xie, Weijia Tong, Yue Gu, Harvest Feng Wu, Liang |
author_sort | Wang, Yuxuan |
collection | PubMed |
description | The clinical features of EBV-positive diffuse large B cell lymphoma (DLBCL) indicate a poorer prognosis than EBV-negative DLBCL. Currently, there is no efficacious drug for EBV-positive DLBCL. The cytokine interleukin-21 (IL-21) has been reported to be pro-apoptotic in DLBCL cell lines and is being explored as a new therapeutic strategy for this type of lymphomas. However, our previous studies showed that IL-21 stimulation of EBV-positive DLBCL cell lines leads to increased proliferation. Here, analysis of a rare clinical sample of EBV-positive DLBCL, in combination with a NOD/SCID mouse xenograft model, confirmed the effect of IL-21 on the proliferation of EBV-positive DLBCL cells. Using RNA-sequencing, we identified the pattern of differentially-expressed genes following IL-21 treatment and verified the expression of key genes at the protein level using western blotting. We found that IL-21 upregulates expression of the host MYC and AP-1 (composed of related Jun and Fos family proteins) and STAT3 phosphorylation, as well as expression of the viral LMP-1 protein. These proteins are known to promote the G1/S phase transition to accelerate cell cycle progression. Furthermore, in NOD/SCID mouse xenograft model experiments, we found that IL-21 treatment increases glucose uptake and angiogenesis in EBV-positive DLBCL tumours. Although more samples are needed to validate these observations, our study reconfirms the adverse effects of IL-21 on EBV-positive DLBCL, which has implications for the drug development of DLBCL. |
format | Online Article Text |
id | pubmed-7378064 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73780642020-07-24 IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma Wang, Yuxuan Wang, Chengcheng Cai, Xiyunyi Mou, Chang Cui, Xueting Zhang, Yingying Ge, Feng Dong, Hao Hao, Yuanyuan Cai, Lei Wu, Shuting Feng, Chenjie Chen, Jiamin Li, Jianyong Xu, Wei Fan, Lei Xie, Weijia Tong, Yue Gu, Harvest Feng Wu, Liang Sci Rep Article The clinical features of EBV-positive diffuse large B cell lymphoma (DLBCL) indicate a poorer prognosis than EBV-negative DLBCL. Currently, there is no efficacious drug for EBV-positive DLBCL. The cytokine interleukin-21 (IL-21) has been reported to be pro-apoptotic in DLBCL cell lines and is being explored as a new therapeutic strategy for this type of lymphomas. However, our previous studies showed that IL-21 stimulation of EBV-positive DLBCL cell lines leads to increased proliferation. Here, analysis of a rare clinical sample of EBV-positive DLBCL, in combination with a NOD/SCID mouse xenograft model, confirmed the effect of IL-21 on the proliferation of EBV-positive DLBCL cells. Using RNA-sequencing, we identified the pattern of differentially-expressed genes following IL-21 treatment and verified the expression of key genes at the protein level using western blotting. We found that IL-21 upregulates expression of the host MYC and AP-1 (composed of related Jun and Fos family proteins) and STAT3 phosphorylation, as well as expression of the viral LMP-1 protein. These proteins are known to promote the G1/S phase transition to accelerate cell cycle progression. Furthermore, in NOD/SCID mouse xenograft model experiments, we found that IL-21 treatment increases glucose uptake and angiogenesis in EBV-positive DLBCL tumours. Although more samples are needed to validate these observations, our study reconfirms the adverse effects of IL-21 on EBV-positive DLBCL, which has implications for the drug development of DLBCL. Nature Publishing Group UK 2020-07-23 /pmc/articles/PMC7378064/ /pubmed/32704112 http://dx.doi.org/10.1038/s41598-020-69227-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Yuxuan Wang, Chengcheng Cai, Xiyunyi Mou, Chang Cui, Xueting Zhang, Yingying Ge, Feng Dong, Hao Hao, Yuanyuan Cai, Lei Wu, Shuting Feng, Chenjie Chen, Jiamin Li, Jianyong Xu, Wei Fan, Lei Xie, Weijia Tong, Yue Gu, Harvest Feng Wu, Liang IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma |
title | IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma |
title_full | IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma |
title_fullStr | IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma |
title_full_unstemmed | IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma |
title_short | IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma |
title_sort | il-21 stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in ebv-positive diffuse large b cell lymphoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378064/ https://www.ncbi.nlm.nih.gov/pubmed/32704112 http://dx.doi.org/10.1038/s41598-020-69227-0 |
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