Alterations of miRNAs and miRNA-regulated mRNA expression in GC B cell lymphomas determined by integrative sequencing analysis.

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Hdl Handle:
http://hdl.handle.net/10033/617314
Title:
Alterations of miRNAs and miRNA-regulated mRNA expression in GC B cell lymphomas determined by integrative sequencing analysis.
Authors:
Hezaveh, Kebria; Kloetgen, Andreas; Bernhart, Stephan H; Mahapatra, Kunal Das; Lenze, Dido; Richter, Julia; Haake, Andrea; Bergmann, Anke K; Brors, Benedikt; Burkhardt, Birgit; Claviez, Alexander; Drexler, Hans G; Eils, Roland; Haas, Siegfried; Hoffmann, Steve; Karsch, Dennis; Klapper, Wolfram; Kleinheinz, Kortine; Korbel, Jan; Kretzmer, Helene; Kreuz, Markus; Küppers, Ralf; Lawerenz, Chris; Leich, Ellen; Loeffler, Markus; Mantovani-Loeffler, Luisa; López, Cristina; McHardy, Alice C; Möller, Peter; Rohde, Marius; Rosenstiel, Philip; Rosenwald, Andreas; Schilhabel, Markus; Schlesner, Matthias; Scholz, Ingrid; Stadler, Peter F; Stilgenbauer, Stephan; Sungalee, Séphanie; Szczepanowski, Monika; Trümper, Lorenz; Weniger, Marc A; Siebert, Reiner; Borkhardt, Arndt; Hummel, Michael; Hoell, Jessica I
Abstract:
MicroRNAs are well-established players in posttranscriptional gene regulation. However, information on the effects of microRNA deregulation mainly relies on bioinformatic prediction of potential targets, whereas proof of the direct physical microRNAs/target mRNAs interaction is mostly lacking. Within the International Cancer Genome Consortium Project Determining Molecular Mechanisms in Malignant Lymphoma by Sequencing (ICGC MMML-Seq), we performed miRnome sequencing from 16 Burkitt lymphomas, 19 diffuse large B-cell lymphomas, and 21 follicular lymphomas. Twenty-two miRNAs separated Burkitt lymphomas from diffuse large B-cell lymphomas/follicular lymphomas, of which 13 have shown regulation by MYC. Moreover, we show expression of three hitherto unreported microRNAs. Additionally, we detect 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 microRNAs with mRNAs, we performed Argonaute-2 photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation experiments. MicroRNAs directly targeted 208 mRNAs in the Burkitt lymphomas and 328 mRNAs 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 uncovers in detail the mRNA deregulation through microRNAs as a highly relevant mechanism in lymphomagenesis.
Affiliation:
Heinrich-Heine-University Duesseldorf, Medical Faculty, Department of Pediatric Oncology
Citation:
Alterations of miRNAs and miRNA-regulated mRNA expression in GC B cell lymphomas determined by integrative sequencing analysis. 2016: Haematologica
Journal:
Haematologica
Issue Date:
6-Jul-2016
URI:
http://hdl.handle.net/10033/617314
DOI:
10.3324/haematol.2016.143891
PubMed ID:
27390358
Type:
Article
ISSN:
1592-8721
Appears in Collections:
publications of the research group bioinformatics in infection research ([BRICS] BIFO)

Full metadata record

DC FieldValue Language
dc.contributor.authorHezaveh, Kebriaen
dc.contributor.authorKloetgen, Andreasen
dc.contributor.authorBernhart, Stephan Hen
dc.contributor.authorMahapatra, Kunal Dasen
dc.contributor.authorLenze, Didoen
dc.contributor.authorRichter, Juliaen
dc.contributor.authorHaake, Andreaen
dc.contributor.authorBergmann, Anke Ken
dc.contributor.authorBrors, Benedikten
dc.contributor.authorBurkhardt, Birgiten
dc.contributor.authorClaviez, Alexanderen
dc.contributor.authorDrexler, Hans Gen
dc.contributor.authorEils, Rolanden
dc.contributor.authorHaas, Siegfrieden
dc.contributor.authorHoffmann, Steveen
dc.contributor.authorKarsch, Dennisen
dc.contributor.authorKlapper, Wolframen
dc.contributor.authorKleinheinz, Kortineen
dc.contributor.authorKorbel, Janen
dc.contributor.authorKretzmer, Heleneen
dc.contributor.authorKreuz, Markusen
dc.contributor.authorKüppers, Ralfen
dc.contributor.authorLawerenz, Chrisen
dc.contributor.authorLeich, Ellenen
dc.contributor.authorLoeffler, Markusen
dc.contributor.authorMantovani-Loeffler, Luisaen
dc.contributor.authorLópez, Cristinaen
dc.contributor.authorMcHardy, Alice Cen
dc.contributor.authorMöller, Peteren
dc.contributor.authorRohde, Mariusen
dc.contributor.authorRosenstiel, Philipen
dc.contributor.authorRosenwald, Andreasen
dc.contributor.authorSchilhabel, Markusen
dc.contributor.authorSchlesner, Matthiasen
dc.contributor.authorScholz, Ingriden
dc.contributor.authorStadler, Peter Fen
dc.contributor.authorStilgenbauer, Stephanen
dc.contributor.authorSungalee, Séphanieen
dc.contributor.authorSzczepanowski, Monikaen
dc.contributor.authorTrümper, Lorenzen
dc.contributor.authorWeniger, Marc Aen
dc.contributor.authorSiebert, Reineren
dc.contributor.authorBorkhardt, Arndten
dc.contributor.authorHummel, Michaelen
dc.contributor.authorHoell, Jessica Ien
dc.date.accessioned2016-07-21T10:51:35Z-
dc.date.available2016-07-21T10:51:35Z-
dc.date.issued2016-07-06-
dc.identifier.citationAlterations of miRNAs and miRNA-regulated mRNA expression in GC B cell lymphomas determined by integrative sequencing analysis. 2016: Haematologicaen
dc.identifier.issn1592-8721-
dc.identifier.pmid27390358-
dc.identifier.doi10.3324/haematol.2016.143891-
dc.identifier.urihttp://hdl.handle.net/10033/617314-
dc.description.abstractMicroRNAs are well-established players in posttranscriptional gene regulation. However, information on the effects of microRNA deregulation mainly relies on bioinformatic prediction of potential targets, whereas proof of the direct physical microRNAs/target mRNAs interaction is mostly lacking. Within the International Cancer Genome Consortium Project Determining Molecular Mechanisms in Malignant Lymphoma by Sequencing (ICGC MMML-Seq), we performed miRnome sequencing from 16 Burkitt lymphomas, 19 diffuse large B-cell lymphomas, and 21 follicular lymphomas. Twenty-two miRNAs separated Burkitt lymphomas from diffuse large B-cell lymphomas/follicular lymphomas, of which 13 have shown regulation by MYC. Moreover, we show expression of three hitherto unreported microRNAs. Additionally, we detect 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 microRNAs with mRNAs, we performed Argonaute-2 photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation experiments. MicroRNAs directly targeted 208 mRNAs in the Burkitt lymphomas and 328 mRNAs 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 uncovers in detail the mRNA deregulation through microRNAs as a highly relevant mechanism in lymphomagenesis.en
dc.languageENG-
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleAlterations of miRNAs and miRNA-regulated mRNA expression in GC B cell lymphomas determined by integrative sequencing analysis.-
dc.typeArticleen
dc.contributor.departmentHeinrich-Heine-University Duesseldorf, Medical Faculty, Department of Pediatric Oncologyen
dc.identifier.journalHaematologicaen

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