{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"contact_person":["Omics & Datamanagment Core Facility"],"full_dataset_link":["https://ega-archive.org/dacs/EGAC00001000381"],"host":["EGA"],"description":["EGA DAC EGAC00001000381"],"repository":["EGA"],"email":["odcf-service@dkfz-heidelberg.de"],"pubmed_abstract":["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.","Despite the established role of the transcription factor MYC in cancer, little is known about the impact of a new class of transcriptional regulators, the long noncoding RNAs (lncRNAs), on MYC ability to influence the cellular transcriptome. Here, we have intersected RNA-sequencing data from two MYC-inducible cell lines and a cohort of 91 B-cell lymphomas with or without genetic variants resulting in MYC overexpression. We identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated in the same direction by MYC in the model cell lines. Among them, we focused on a lncRNA that we named MYC-induced long noncoding RNA (MINCR), showing a strong correlation with MYC expression in MYC-positive lymphomas. To understand its cellular role, we performed RNAi and found that MINCR knockdown is associated with an impairment in cell cycle progression. Differential gene expression analysis after RNAi showed a significant enrichment of cell cycle genes among the genes down-regulated after MINCR knockdown. Interestingly, these genes are enriched in MYC binding sites in their promoters, suggesting that MINCR acts as a modulator of the MYC transcriptional program. Accordingly, MINCR knockdown was associated with a reduction in MYC binding to the promoters of selected cell cycle genes. Finally, we show that down-regulation of Aurora kinases A and B and chromatin licensing and DNA replication factor 1 may explain the reduction in cellular proliferation observed on MINCR knockdown. We, therefore, suggest that MINCR is a newly identified player in the MYC transcriptional network able to control the expression of cell cycle genes."],"pubmed_title":["Alterations of microRNA and microRNA-regulated messenger RNA expression in germinal center B-cell lymphomas determined by integrative sequencing analysis.","MINCR is a MYC-induced lncRNA able to modulate MYC's transcriptional network in Burkitt lymphoma cells."],"pubmed_authors":["Hezaveh Kebria K, Kloetgen Andreas A, Bernhart Stephan H SH, Mahapatra Kunal Das KD, Lenze Dido D, Richter Julia J, Haake Andrea A, Bergmann Anke K AK, Brors Benedikt B, Burkhardt Birgit B, Claviez Alexander A, Drexler Hans G HG, Eils Roland R, Haas Siegfried S, Hoffmann Steve S, Karsch Dennis D, Klapper Wolfram W, Kleinheinz Kortine K, Korbel Jan J, Kretzmer Helene H, Kreuz Markus M, Küppers Ralf R, Lawerenz Chris C, Leich Ellen E, Loeffler Markus M, Mantovani-Loeffler Luisa L, López Cristina C, McHardy Alice C AC, Möller Peter P, Rohde Marius M, Rosenstiel Philip P, Rosenwald Andreas A, Schilhabel Markus M, Schlesner Matthias M, Scholz Ingrid I, Stadler Peter F PF, Stilgenbauer Stephan S, Sungalee Stéphanie S, Szczepanowski Monika M, Trümper Lorenz L, Weniger Marc A MA, Siebert Reiner R, Borkhardt Arndt A, Hummel Michael M, Hoell Jessica I JI","Doose Gero G, Haake Andrea A, Bernhart Stephan H SH, López Cristina C, Duggimpudi Sujitha S, Wojciech Franziska F, Bergmann Anke K AK, Borkhardt Arndt A, Burkhardt Birgit B, Claviez Alexander A, Dimitrova Lora L, Haas Siegfried S, Hoell Jessica I JI, Hummel Michael M, Karsch Dennis D, Klapper Wolfram W, Kleo Karsten K, Kretzmer Helene H, Kreuz Markus M, Küppers Ralf R, Lawerenz Chris C, Lenze Dido D, Loeffler Markus M, Mantovani-Löffler Luisa L, Möller Peter P, Ott German G, Richter Julia J, Rohde Marius M, Rosenstiel Philip P, Rosenwald Andreas A, Schilhabel Markus M, Schneider Markus M, Scholz Ingrid I, Stilgenbauer Stephan S, Stunnenberg Hendrik G HG, Szczepanowski Monika M, Trümper Lorenz L, Weniger Marc A MA, Hoffmann Steve S, Siebert Reiner R, Iaccarino Ingram I"],"name_synonyms":["Line, Cell Lines, Cell., associated, Cell, Lines"],"pubmed_title_synonyms":["germinal center B-lymphocyte, RNA, GC B cell, determination, Polyadenylated, stRNA, Small Temporal RNA, Messenger RNA, Primary, GC B lymphocyte, Small, Micro RNA, GC B-cell, Messenger, Poly(A)+ mRNA, INSDC_feature:mRNA, Polyadenylated RNA, pre-miRNA, Non Polyadenylated, pri miRNA, Polyadenylated Messenger RNA, miRNAs, Poly(A)+ RNA, Small Temporal, Non Polyadenylated mRNA, protein_coding_transcript, germinal center B-cell, Micro, mRNA, Poly(A) Tail, Temporal RNA, Polyadenylated Messenger, germinal center B lymphocyte, Non-Polyadenylated, chemical analysis., messenger RNA, Primary MicroRNA, miRNA, Primary miRNA, INSDC_feature:ncRNA, pri-miRNA, Non-Polyadenylated mRNA, template RNA, MicroRNA, GC B-lymphocyte, assay, Polyadenylated mRNA, pre miRNA, Poly(A) RNA"],"pubmed_abstract_synonyms":["Ribonucleic, RAS, Ras, PRKBA, l(1)G0098, Akt/PKB, dP60, Vps34, acetylglucosaminyltransferase-like protein, Nodular Histiocytic Lymphomas, DAKT1/PKB, BcDNA:LD15217, MYC, Myc, Germinoblastoma, Tumor, Ras-1, AKT1, VPS34, MIRN-142-3p, 11621, Social Controls, B430311C09Rik, Mutations, PI-3 kinase, B Cell, p110-alpha, Small, ras, c-ras2, Bio Informatics, EG:BACN5I9.1, myc, myd, Lymphomas, Non Polyadenylated, Follicular, Histiocytic Lymphoma, Divorced, Dp60, like-acetylglucosaminyltransferase, Genomes, BL, PI3K_59F, dm/dMyc, Mbp-1, PI3-kinase activity, Small Follicular Center Cell, Divorces, Burkitt's tumour [obs], miRNA, PI3Kgamma, Computational, RacPK, Social, MCAP, PI3K 68D, Mixed Lymphocytic-Histiocytic, Giant Follicular, Precipitations, Computational Molecular Biologies, ATP - 1-phosphatidyl-1D-myo-inositol 3-phosphotransferase activity, CG1799, Tumors, Giant Follicular Lymphoma, dVps34, B-Cell Lymphoma, Small Lymphoid, Ras2, RAS2, Data Set, dmyc1, Polyadenylated, Ras1, RAS1, Follicular Large Cell, rea, Biologies, p50alpha, Burkitt Leukemia, MIRN376 microRNA, CG2699, Computational Molecular, DmelCG5373, AKT/PKB, Burkitts lymphoma, Benign, C530050K14, Dm, Giant Follicular Lymphomas, mKIAA0609, Computational Molecular Biology, type-1 PI3K, dRas85D, p-Akt, Primary., Ribonucleic acids, L3 Lymphocytic Leukemias, mMyc, ras1, pre-miRNA, Nodular Lymphoma, Burkitts Lymphoma, ras2, BcDNA:RE36103, pri miRNA, Polyadenylated Messenger RNA, fg, Acid, CG11621, miRNAs, Burkitt's lymphoma of unspecified site (disorder), Non Polyadenylated mRNA, protein_coding_transcript, Hras-1, Benign Neoplasms, Dm Ras1, whole genome, MLYM, Germinoblastomas, Controls, dAKT/dPKB, PKB/dAKT, DmelCG4141, Non-Polyadenylated mRNA, D-Myc, human, F8A5_4, regulation of protein expression, Malignant Neoplasms, APDS, Follicular Mixed-Cell Lymphomas, MDC1D, Brill-Symmers Disease, RasI, enr, Nodular Histiocytic, Lymphoma, PI3KBETA, Follicular Large-Cell, MicroRNA, Poorly Differentiated, dMyc1, Burkitt's lymphoma NOS (disorder), Poly(A) RNA, Harvey-ras, Hras1, RAC-ALPHA, Regulations, CG10798, DmelCG4006, Large Follicular Center-Cell, dm/myc, stRNA, Neoplasms, dRas, CG1167, H-ras, DRAS1, DRas2, IMPDH, LARGE1, dMyc, dMYC, LD06825, regulation of gene product expression, Dras2, Dras1, PIK3, Large Lymphoid Lymphoma, D-Ras, dVps34/PI3K59F, Pi3Kp60, PI3K-dp110, Immune Precipitations, Gene Products, Kras-2, Nop30, dPI3K, bHLHe57, anon-92Ed, IMPdH, Ha-ras, Immune Precipitation, Dras, class I, ras 1, Sarcomas, Follicular Lymphomas, Leukemia, MDDGB6, raspberry/impd, MAPK signaling, Mixed-Cell Lymphomas, Dmyc, DMYc, messenger RNA, microRNA 376c, Ras[V12], Pi3Kp110, EK3-4, Small Follicular Center-Cell, DRas, P110BETA, Neoplasias, DRas85D/Ras, Dmras64B, Large-Cell, template RNA, L3, PI3K21B, Nird, RNCMYC, Poorly-Differentiated, AKT, Akt, MCM, bHLHe39, pre miRNA, dmyc, Cancer, Cpk, RNA, Malignant Neoplasm, Burkitts Leukemia, AA414921, akt, class II, Large-Cell Lymphomas, type III phosphoinositide 3-kinase activity, Burkitt Cell Leukemia, Messenger RNA, RNS, DAkt1, Primary, DAKT1, hsa-mir-142, D-ras-1, PI(3)K, cpk, E(faf), Burkitt Cell, PI3K-92E/Dp110, Small and Large Cleaved Cell, DmelCG1167, PIK3C1, Mixed Lymphocytic Histiocytic, PKB, MT, CWS6, CWS5, Social Control, Burkitt Lymphoma, Poly(A)+ mRNA, chemical analysis, PKB-ALPHA, Neoplasm, S35097, INSDC_feature:mRNA, Germinoblastic Sarcomas, CG4006, gene regulation, Mixed Cell, Brill Symmers Disease, Giant, hsa-mir-376, Dakt1, RAS85D, primary cancer, Dmras85D, mRNA, l(1)9Eb, Histiocytic, Temporal RNA, Separations, Burkitt's Tumor, Cancers, Ribonucleic Acid, DmelCG11621, Small Cleaved Cell, malignant tumor, B Cell Lymphoma, Grade 1, Grade 2, Grade 3, caPI3K, dAkt/PKB, CLOVE, Burkitt's type, like-glycosyltransferase, DmVps34, IMD14, PI3K_68D, PI3K-92D, Burkitt's tumor or lymphoma, regulation, Dmp110, Polyadenylated mRNA, Neoplasia, Small Cleaved-Cell Lymphoma, Co-Immunoprecipitations, African Lymphoma, Ras1/RAs85D, CG5373, Burkitt-Type, determination, ATVPS34, ERK/MAPK cascade, Mbp1, myc-B, c-rasHa, PI3K, DmelCG10798, E(sev)3C, Dp110, Molecular Biologies, Small Follicular Center-Cell Lymphoma, Brill-Symmers, CG11485, Small Cleaved-Cell, Co Immunoprecipitation, Malignant Lymphomas, c-MYC, c-Myc, PHOSPHATIDYLINOSITOL 3-KINASE, Follicular Large-Cell Lymphomas, DmelCG2699, F8A5.4, ARC, p110alpha, phosphatidylinositol 3-kinase activity, Mixed-Cell Lymphoma, Formal Social Controls, D-Ras1, RNA Gene Products, Reticulolymphosarcoma, Mixed Small and Large Cell, c-myc, miR-376c, Small Temporal, Burkitt, RTK, Biology, Pi3K92D, CG4141, Burkitt Tumor, Burkitt lymphoma/leukaemia, Polyadenylated Messenger, Co-Immunoprecipitation, l(1)G0436, catalyst activity, Precipitation, Nodular Large Follicular Center-Cell Lymphoma, Pi3k, ras85B, Follicular Mixed-Cell Lymphoma, ras85D, Primary miRNA, PI[[3]]K, Bio-Informatic, INSDC_feature:ncRNA, pri-miRNA, PKB|Akt, small Non-Cleaved cell Lymphoma, Malignant Lymphoma, Large Cell Lymphoma, Sarcoma, Immune, D-ras-2, p55alpha, Large Follicular Center Cell, malignant neoplasm, Bio-Informatics, MAPKKK cascade during sporulation, Malignancies, Pi3K, PI3k, MCMTC, l(3)s1747, PI3K68D, dakt, AU016757, gyltl1b-b, ribose nucleic acid, Ki-ras, P110DELTA, Burkitt's tumor NOS (morphologic abnormality), PtdIns-3-kinase activity, ribonucleic acids, Small Temporal RNA, microRNA-142, l(3)89Bq, vacuolar protein sorting 34, dPIK, 1-phosphatidylinositol 3-kinase activity, PKB/Akt, PKB/AKT, Reticulolymphosarcomas, dAkt, dAKT, MDDGA6, Ribonukleinsaeure, NOP, Nodular Lymphomas, pentosenucleic acids, miR-142-3p, microRNA-376, p21[Ras1], Germinoblastic, Nodular Histiocytic Lymphoma, dRas1, dRAS1, KIAA0609, DAkt, Dras85D, acetylglucosaminyltransferase-like 1A, Large-Cell Lymphoma, ras-2, l(3)04226, l(1)G0354, DPKB, l(1)G0351, gyltl1b, LD02673, Bioinformatic, pAkt, Micro, p85alpha, DmelCG1799, c-Ha-ras, l(1)G0359, D-ras1, l(1)G0238, Burkitts Tumor, D-ras2, mdc1d, Control, C-ras1, Dras64B, PI3K 68_D, d-myc, LARGE_HUMAN, C-ras2, l(3)06677, Myc2, l(1)G0002, Niard, l(1)G0482, p110D, Dakt, myc2, c-H-ras, MAPK signalling, l(1)G0127, dPKB, Follicular Large Cell Lymphoma, p120-PI3K, MRTL, Regulation, Burkitt's tumors (morphologic abnormality), droPIK57, Follicular Mixed Cell Lymphoma, DRAC-PK85, Lymphocytic Leukemia, RasV12, l(1)G0139, PI3K92E, Kras2, Benign Neoplasm, B-Cell, Pi3K_59F, DmelCG9375, type I phosphatidylinositol kinase activity, Malignant, Germinoblastic Sarcoma, froggy, Gyltl1a, phosphatidylinositol 3-kinase, l(1)G0388, Dpkb, Nodular Large Follicular Center Cell Lymphoma, anon-WO03040301.171, MYCC, Burkitt's Lymphoma, Messenger, p60, Small Cleaved Cell Lymphoma, c-myc II, PHOSPATIDYLINOSITOL 3-KINASE, Separated, l(1)G0380, Dp110/PI3K, PI3K-68D/E, p21B, Lymphocytic, dras1, Dm-ras-64B, Malignancy, LARGE, PI3'K, Mixed Cell Lymphoma, l(1)G0391, Follicular Large-Cell Lymphoma, Non-Polyadenylated RNA, BHLHE39, BPFD#36, Ras 85D, PI3K-68D, Mixed Small and Large Lymphoid, Histiocytic Lymphomas, Nodular, L3 Lymphocytic, DRAC-PK, Follicular Lymphoma, ras-l, Burkitt's, l(1)G0056, dP110, Molecular Biology, Disease, 6330412C24Rik, Formal Social Control, CG9375, p120, Follicular Mixed-Cell, p110, miR-142, K-ras, Vps34p, Small and Large Cleaved-Cell, Bioinformatics, fs(3)05703, ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase activity, Micro RNA, L3 Lymphocytic Leukemia, vps34, EP(X)1093, yeast nucleic acid, Burkitt's lymphoma - disorder, dp110, D-Akt, Burkitt's tumor, Polyadenylated RNA, AI929937, PI3CG, Large Cell, malignant lymphoma, PI-3-K, ribonucleic acid, Separation, PI3K-59F, Poly(A)+ RNA, Poly(A) Tail, PI3K-Dp110, akt1, dAkt1, Burkitt's Leukemia, Non Polyadenylated RNA, DRAC-PK66, Non-Polyadenylated, Lymphoblastic, class III, Primary MicroRNA, p110gamma, Su(tor)3-2, dakt1, Lymphocytic Lymphoma, Small Follicular Center Cell Lymphoma, B-Cell Lymphomas, PKBalpha, African, dAKT1, assay, RAC, Rac, miR-376, Large Lymphoid, Mixed-Cell, glycosyltransferase-like protein LARGE1"],"additional_accession":[]},"is_claimable":false,"name":"MMML associated cell line data","description":"Data Access Committee EGAC00001000381","dates":{"output":"2025-1-9"},"accession":"EGAC00001000381","cross_references":{"TAXONOMY":["9606"],"pubmed":["26351698","27390358"],"EGA":["EGAS00001001199","EGAS00001001394","EGAS00001004019","EGAD00001001612","EGAD00001005504","EGAD00001001598","EGAD00001001468"]}}