Alterations of microRNA and microRNA-regulated messenger RNA expression in germinal center B-cell lymphomas determined by integrative sequencing analysis
MicroRNA are well-established players in post-transcriptional gene regulation. However, information on the effects of microRNA deregulation mainly relies on bioinformatic prediction of potential targets, whereas proof of the direct physical microRNA/target messenger RNA interaction is mostly lacking...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
July 6, 2016
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| In: |
Haematologica
Year: 2016, Jahrgang: 101, Heft: 11, Pages: 1380-1389 |
| ISSN: | 1592-8721 |
| DOI: | 10.3324/haematol.2016.143891 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3324/haematol.2016.143891 Verlag, lizenzpflichtig, Volltext: http://www.haematologica.org/content/101/11/1380 
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| Verfasserangaben: | Kebria Hezaveh, Andreas Kloetgen, Stephan H. Bernhart, Kunal Das Mahapatra, Dido Lenze, Julia Richter, Andrea Haake, Anke K. Bergmann, Benedikt Brors, Birgit Burkhardt, Alexander Claviez, Hans G. Drexler, Roland Eils, Siegfried Haas, Steve Hoffmann, Dennis Karsch, Wolfram Klapper, Kortine Kleinheinz, Jan Korbel, Helene Kretzmer, Markus Kreuz, Ralf Küppers, Chris Lawerenz, Ellen Leich, Markus Loeffler, Luisa Mantovani-Loeffler, Cristina López, Alice C. McHardy, Peter Möller, Marius Rohde, Philip Rosenstiel, Andreas Rosenwald, Markus Schilhabel, Matthias Schlesner, Ingrid Scholz, Peter F. Stadler, Stephan Stilgenbauer, Stéphanie Sungalee, Monika Szczepanowski, Lorenz Trümper, Marc A. Weniger, Reiner Siebert, Arndt Borkhardt, Michael Hummel, Jessica I. Hoell |
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| 245 | 1 | 0 | |a Alterations of microRNA and microRNA-regulated messenger RNA expression in germinal center B-cell lymphomas determined by integrative sequencing analysis |c Kebria Hezaveh, Andreas Kloetgen, Stephan H. Bernhart, Kunal Das Mahapatra, Dido Lenze, Julia Richter, Andrea Haake, Anke K. Bergmann, Benedikt Brors, Birgit Burkhardt, Alexander Claviez, Hans G. Drexler, Roland Eils, Siegfried Haas, Steve Hoffmann, Dennis Karsch, Wolfram Klapper, Kortine Kleinheinz, Jan Korbel, Helene Kretzmer, Markus Kreuz, Ralf Küppers, Chris Lawerenz, Ellen Leich, Markus Loeffler, Luisa Mantovani-Loeffler, Cristina López, Alice C. McHardy, Peter Möller, Marius Rohde, Philip Rosenstiel, Andreas Rosenwald, Markus Schilhabel, Matthias Schlesner, Ingrid Scholz, Peter F. Stadler, Stephan Stilgenbauer, Stéphanie Sungalee, Monika Szczepanowski, Lorenz Trümper, Marc A. Weniger, Reiner Siebert, Arndt Borkhardt, Michael Hummel, Jessica I. Hoell |
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| 520 | |a MicroRNA are well-established players in post-transcriptional gene regulation. However, information on the effects of microRNA deregulation mainly relies on bioinformatic prediction of potential targets, whereas proof of the direct physical microRNA/target messenger RNA interaction is mostly lacking. Within the International Cancer Genome Consortium Project “Determining Molecular Mechanisms in Malignant Lymphoma by Sequencing”, we performed miRnome sequencing from 16 Burkitt lymphomas, 19 diffuse large B-cell lymphomas, and 21 follicular lymphomas. Twenty-two miRNA separated Burkitt lymphomas from diffuse large B-cell lymphomas/follicular lymphomas, of which 13 have shown regulation by MYC. Moreover, we found expression of three hitherto unreported microRNA. Additionally, we detected recurrent mutations of hsa-miR-142 in diffuse large B-cell lymphomas and follicular lymphomas, and editing of the hsa-miR-376 cluster, providing evidence for microRNA editing in lymphomagenesis. To interrogate the direct physical interactions of microRNA with messenger RNA, we performed Argonaute-2 photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation experiments. MicroRNA directly targeted 208 messsenger RNA in the Burkitt lymphomas and 328 messenger RNA in the non-Burkitt lymphoma models. This integrative analysis discovered several regulatory pathways of relevance in lymphomagenesis including Ras, PI3K-Akt and MAPK signaling pathways, also recurrently deregulated in lymphomas by mutations. Our dataset reveals that messenger RNA deregulation through microRNA is a highly relevant mechanism in lymphomagenesis. | ||
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