IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma.

Animals Apoptosis / drug effects Biomarkers, Tumor / metabolism Cell Cycle / drug effects Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects Gene Expression Regulation, Neoplastic / drug effects Gene Ontology Gene Regulatory Networks Herpesvirus 4, Human / physiology Humans Interleukins / pharmacology Lymphoma, Large B-Cell, Diffuse / genetics Mice, Inbred NOD Mice, SCID Models, Biological Neovascularization, Pathologic / genetics Proto-Oncogene Proteins c-myc / genetics Up-Regulation / drug effects Xenograft Model Antitumor Assays

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
23 07 2020
Historique:
received: 23 01 2020
accepted: 08 07 2020
entrez: 25 7 2020
pubmed: 25 7 2020
medline: 15 12 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41598-020-69227-0 PMID: 32704112 PMC: PMC7378064
pubmed: 32704112
doi: 10.1038/s41598-020-69227-0
pii: 10.1038/s41598-020-69227-0
pmc: PMC7378064
doi:

Substances chimiques

Biomarkers, Tumor 0
Interleukins 0
MYC protein, human 0
Proto-Oncogene Proteins c-myc 0
interleukin-21 MKM3CA6LT1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

12326

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Auteurs

Yuxuan Wang (Y)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Chengcheng Wang (C)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Xiyunyi Cai (X)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Chang Mou (C)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Xueting Cui (X)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Yingying Zhang (Y)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Feng Ge (F)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Hao Dong (H)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Yuanyuan Hao (Y)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Lei Cai (L)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Shuting Wu (S)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Chenjie Feng (C)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Jiamin Chen (J)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

Jianyong Li (J)

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China.

Wei Xu (W)

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China.

Lei Fan (L)

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China. fanlei3014@126.com.

Weijia Xie (W)

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, China.

Yue Tong (Y)

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing, China.
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.

Harvest Feng Gu (HF)

School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.

Liang Wu (L)

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China. 1020132373@cpu.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › IL-21 Stimulates the expression and activation...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › IL-21 Stimulates the expression and activation...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › IL-21 Stimulates the expression and activation...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Cycle cellulaire › IL-21 Stimulates the expression and activation...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › IL-21 Stimulates the expression and activation...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › IL-21 Stimulates the expression and activation...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Survie cellulaire › IL-21 Stimulates the expression and activation...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › IL-21 Stimulates the expression and activation...
questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Vocabulaire contrôlé › Ontologies biologiques › Gene Ontology › IL-21 Stimulates the expression and activation...
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questionsmedicales.fr › Virus › Virus oncogènes › Virus tumoraux à ADN › Gammaherpesvirinae › Lymphocryptovirus › Herpèsvirus humain de type 4 › IL-21 Stimulates the expression and activation...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › IL-21 Stimulates the expression and activation...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › IL-21 Stimulates the expression and activation...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Syndromes lymphoprolifératifs › Lymphomes › Lymphome malin non hodgkinien › Lymphome B › Lymphome B diffus à grandes cellules › IL-21 Stimulates the expression and activation...
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questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique hélice-boucle-hélice › Protéines proto-oncogènes c-myc › IL-21 Stimulates the expression and activation...
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