6533b828fe1ef96bd1288fc2

RESEARCH PRODUCT

Virus-encoded microRNA contributes to the molecular profile of EBV-positive Burkitt lymphomas

Cristiana BellanEmily A RogenaMaria Rosaria SapienzaMaria Raffaella AmbrosioDavide GibelliniStefano LazziLynnette K TumwineMaria Antonella LaginestraMohsen NavariMohsen NavariGiulia De FalcoGiulia De FalcoFabio FuligniPier Paolo PiccalugaJessica ConsiglioMaura RossiMaryam EtebariCarlo M. CroceLorenzo LeonciniStefano PileriClaudio Tripodo

subject

0301 basic medicineBART6; Burkitt lymphoma; EBV; miRNA; pathogenesisEpstein-Barr Virus InfectionsHerpesvirus 4 HumanpathogenesiRNA-binding proteinRNA-Binding ProteinEpstein-Barr Virus Infectionhemic and lymphatic diseasesCluster AnalysisViralOligonucleotide Array Sequence AnalysisGeneticsBART6; Burkitt lymphoma; EBV; miRNA; pathogenesis; Burkitt Lymphoma; Cluster Analysis; Cytoskeletal Proteins; Epstein-Barr Virus Infections; Gene Expression Profiling; Gene Expression Regulation Neoplastic; Gene Expression Regulation Viral; Herpesvirus 4 Human; Host-Pathogen Interactions; Humans; Immunohistochemistry; MicroRNAs; Neoplasm Proteins; Oligonucleotide Array Sequence Analysis; Phospholipase C delta; RNA Viral; RNA-Binding Proteins; Reverse Transcriptase Polymerase Chain Reaction; ras Proteins; OncologyReverse Transcriptase Polymerase Chain ReactionpathogenesisMicrofilament ProteinsIntracellular Signaling Peptides and ProteinsBurkitt lymphomaRNA-Binding ProteinsMicroRNAPhenotypeImmunohistochemistryNeoplasm ProteinsHost-Pathogen InteractionGene Expression Regulation NeoplasticOncologyHost-Pathogen InteractionsRNA ViralHumanResearch PaperGene Expression Regulation ViralBART6BiologySettore MED/08 - Anatomia PatologicaVirusNeoplasm Protein03 medical and health sciencesEBVmicroRNACytoskeletal ProteinmedicineHumansEpstein–Barr virus infectionGenemiRNANeoplasticCluster AnalysiOligonucleotide Array Sequence AnalysiGene Expression ProfilingHerpesvirus 4ras Proteinmedicine.diseaseLymphomaGene expression profilingCytoskeletal ProteinsMicroRNAs030104 developmental biologyGene Expression Regulationras ProteinsRNABART6; EBV; burkitt lymphoma; miRNA; pathogenesisPhospholipase C delta

description

Burkitt lymphoma (BL) is an aggressive neoplasm characterized by consistent morphology and phenotype, typical clinical behavior and distinctive molecular profile. The latter is mostly driven by the MYC over-expression associated with the characteristic translocation (8;14) (q24; q32) or with variant lesions. Additional genetic events can contribute to Burkitt Lymphoma pathobiology and retain clinical significance. A pathogenetic role for Epstein-Barr virus infection in Burkitt lymphomagenesis has been suggested; however, the exact function of the virus is largely unknown. In this study, we investigated the molecular profiles (genes and microRNAs) of Epstein-Barr virus-positive and -negative BL, to identify specific patterns relying on the differential expression and role of Epstein-Barr virus-encoded microRNAs. First, we found significant differences in the expression of viral microRNAs and in selected target genes. Among others, we identified LIN28B, CGNL1, GCET2, MRAS, PLCD4, SEL1L, SXX1, and the tyrosine kinases encoding STK10/STK33, all provided with potential pathogenetic significance. GCET2, also validated by immunohistochemistry, appeared to be a useful marker for distinguishing EBV-positive and EBV-negative cases. Further, we provided solid evidences that the EBV-encoded microRNAs (e.g. BART6) significantly mold the transcriptional landscape of Burkitt Lymphoma clones. In conclusion, our data indicated significant differences in the transcriptional profiles of EBV-positive and EBV-negative BL and highlight the role of virus encoded miRNA.

yearjournalcountryeditionlanguage
2015-07-01Oncotarget
http://europepmc.org/articles/PMC4807994