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Interleukin 21 controls mRNAand MicroRNA expression in CD40-activated chronic lymphocytic leukemia cells
dc.creator | De Cecco L., Capaia M., Zupo S., Cutrona G., Matis S., Brizzolara A., Orengo A.M., Croce M., Marchesi E., Ferrarini M., Canevari S., Ferrini S., Speletas M. | en |
dc.date.accessioned | 2023-01-31T07:51:52Z | |
dc.date.available | 2023-01-31T07:51:52Z | |
dc.date.issued | 2015 | |
dc.identifier | 10.1371/journal.pone.0134706 | |
dc.identifier.issn | 19326203 | |
dc.identifier.uri | http://hdl.handle.net/11615/73131 | |
dc.description.abstract | Several factors support CLL cell survival in the microenvironment. Under different experimental conditions, IL21 can either induce apoptosis or promote CLL cell survival. To investigate mechanisms involved in the effects of IL21, we studied the ability of IL21 to modulate gene and miRNA expressions in CD40-activated CLL cells. IL21 was a major regulator of chemokine production in CLL cells and it modulated the expression of genes involved in cell movement, metabolism, survival and apoptosis. In particular, IL21 down-regulated the expression of the chemokine genes CCL4, CCL3, CCL3L1, CCL17, and CCL2, while it up-regulated the Th1-related CXCL9 and CXCL10. In addition, IL21 down-regulated the expression of genes encoding signaling molecules, such as CD40, DDR1 and PIK3CD. IL21 modulated a similar set of genes in CLL and normal B-cells (e.g. chemokine genes), whereas other genes, including MYC, TNF, E2F1, EGR2 and GAS-6, were regulated only in CLL cells. An integrated analysis of the miRNome and gene expression indicated that several miRNAs were under IL21 control and these could, in turn, influence the expression of potential target genes. We focused on hsa-miR-663b predicted to down-regulate several relevant genes. Transfection of hsa-miR-663b or its specific antagonist showed that this miRNA regulated CCL17, DDR1, PIK3CD and CD40 gene expression. Our data indicated that IL21 modulates the expression of genes mediating the crosstalk between CLL cells and their microenvironment and miRNAs may take part in this process. © 2015 De Cecco et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en |
dc.language.iso | en | en |
dc.source | PLoS ONE | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84943192178&doi=10.1371%2fjournal.pone.0134706&partnerID=40&md5=a9efa88b12679d2d874ac64d7fd2071a | |
dc.subject | CD40 antigen | en |
dc.subject | chemokine | en |
dc.subject | CXCL9 chemokine | en |
dc.subject | early growth response factor 2 | en |
dc.subject | gamma interferon inducible protein 10 | en |
dc.subject | growth arrest specific protein 6 | en |
dc.subject | interleukin 21 | en |
dc.subject | macrophage inflammatory protein 1alpha | en |
dc.subject | macrophage inflammatory protein 1beta | en |
dc.subject | messenger RNA | en |
dc.subject | microRNA | en |
dc.subject | monocyte chemotactic protein 1 | en |
dc.subject | thymus and activation regulated chemokine | en |
dc.subject | transcription factor E2F1 | en |
dc.subject | tumor necrosis factor | en |
dc.subject | CD40 antigen | en |
dc.subject | chemokine | en |
dc.subject | interleukin 21 | en |
dc.subject | interleukin derivative | en |
dc.subject | messenger RNA | en |
dc.subject | microRNA | en |
dc.subject | MIRN663 microRNA, human | en |
dc.subject | apoptosis | en |
dc.subject | Article | en |
dc.subject | cell metabolism | en |
dc.subject | cell motion | en |
dc.subject | cell survival | en |
dc.subject | chronic lymphatic leukemia | en |
dc.subject | controlled study | en |
dc.subject | down regulation | en |
dc.subject | gene control | en |
dc.subject | gene expression | en |
dc.subject | genetic code | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | leukemia cell | en |
dc.subject | microenvironment | en |
dc.subject | oncogene myc | en |
dc.subject | Th1 cell | en |
dc.subject | upregulation | en |
dc.subject | 3T3 cell line | en |
dc.subject | animal | en |
dc.subject | B lymphocyte | en |
dc.subject | biology | en |
dc.subject | chronic lymphatic leukemia | en |
dc.subject | drug effects | en |
dc.subject | gene expression profiling | en |
dc.subject | gene expression regulation | en |
dc.subject | gene regulatory network | en |
dc.subject | genetics | en |
dc.subject | immunology | en |
dc.subject | lymphocyte activation | en |
dc.subject | metabolism | en |
dc.subject | mouse | en |
dc.subject | prognosis | en |
dc.subject | time factor | en |
dc.subject | Animals | en |
dc.subject | Antigens, CD40 | en |
dc.subject | B-Lymphocytes | en |
dc.subject | Chemokines | en |
dc.subject | Computational Biology | en |
dc.subject | Gene Expression Profiling | en |
dc.subject | Gene Expression Regulation, Leukemic | en |
dc.subject | Gene Regulatory Networks | en |
dc.subject | Humans | en |
dc.subject | Interleukins | en |
dc.subject | Leukemia, Lymphocytic, Chronic, B-Cell | en |
dc.subject | Lymphocyte Activation | en |
dc.subject | Mice | en |
dc.subject | MicroRNAs | en |
dc.subject | NIH 3T3 Cells | en |
dc.subject | Prognosis | en |
dc.subject | RNA, Messenger | en |
dc.subject | Time Factors | en |
dc.subject | Public Library of Science | en |
dc.title | Interleukin 21 controls mRNAand MicroRNA expression in CD40-activated chronic lymphocytic leukemia cells | en |
dc.type | journalArticle | en |
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