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

Oncotarget. 2016 Jan 5;7(1):224-40. doi: 10.18632/oncotarget.4399.

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.

Keywords: BART6; Burkitt lymphoma; EBV; miRNA; pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Burkitt Lymphoma / genetics*
  • Burkitt Lymphoma / virology
  • Cluster Analysis
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Epstein-Barr Virus Infections / genetics*
  • Epstein-Barr Virus Infections / virology
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Regulation, Viral
  • Herpesvirus 4, Human / genetics*
  • Herpesvirus 4, Human / physiology
  • Host-Pathogen Interactions / genetics
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs / genetics*
  • Microfilament Proteins
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phospholipase C delta / genetics
  • Phospholipase C delta / metabolism
  • RNA, Viral / genetics*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • CGNL1 protein, human
  • Cytoskeletal Proteins
  • GCSAM protein, human
  • Intracellular Signaling Peptides and Proteins
  • LIN28B protein, human
  • MRAS protein, human
  • MicroRNAs
  • Microfilament Proteins
  • Neoplasm Proteins
  • RNA, Viral
  • RNA-Binding Proteins
  • PLCD4 protein, human
  • Phospholipase C delta
  • ras Proteins