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

Pier Paolo Piccaluga, Mohsen Navari, Giulia de Falco, Maria Raffaella Ambrosio, Stefano Lazzi, Fabio Fuligni, Cristiana Bellan, Maura Rossi, Maria Rosaria Sapienza, Maria Antonella Laginestra, Maryam Etebari, Emily A Rogena, Lynnette K. Tumwine, Claudio Tripodo, Davide Gibellini, Jessica Consiglio, Carlo M. Croce, Stefano A Pileri, Lorenzo Leoncini

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)224-40
Number of pages17
JournalOncotarget
Volume7
Issue number1
DOIs
Publication statusPublished - Jan 5 2016

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Keywords

  • 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
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Piccaluga, P. P., Navari, M., de Falco, G., Ambrosio, M. R., Lazzi, S., Fuligni, F., Bellan, C., Rossi, M., Sapienza, M. R., Laginestra, M. A., Etebari, M., Rogena, E. A., Tumwine, L. K., Tripodo, C., Gibellini, D., Consiglio, J., Croce, C. M., Pileri, S. A., & Leoncini, L. (2016). Virus-encoded microRNA contributes to the molecular profile of EBV-positive Burkitt lymphomas. Oncotarget, 7(1), 224-40. https://doi.org/10.18632/oncotarget.4399