Dysregulation of global microRNA expression in splenic marginal zone lymphoma and influence of chronic hepatitis C virus infection

J. Peveling-Oberhag, G. Crisman, A. Schmidt, C. Döring, M. Lucioni, L. Arcaini, S. Rattotti, S. Hartmann, A. Piiper, W. P. Hofmann, M. Paulli, R. Küppers, S. Zeuzem, M. L. Hansmann

Research output: Contribution to journalArticlepeer-review

Abstract

The precise molecular pathogenesis of splenic marginal zone lymphoma (SMZL) is still unknown. Clinical and epidemiological data suggest that chronic hepatitis C virus (HCV) infection may have an etiological role in a subset of cases.We performed a large-scale microRNA (miRNA) expression profiling analysis of 381 miRNAs by quantitative reverse transcription PCR (Q-RT-PCR) of 26 microdissected splenic tissue samples (7 HCV SMZL; 8 HCV SMZL and 11 non-neoplastic splenic controls). Single assay Q-RT-PCR and miRNA in situ hybridization (miRNA-ISH) were used to confirm the results in an independent cohort. Unsupervised hierarchical clustering of miRNA expression profiles demonstrated a distinct signature of SMZL compared with the normal splenic marginal zone. Supervised analysis revealed differentially expressed miRNAs, including miRNAs with previously recognized tumor suppressive or oncogenic potential. Five miRNAs were found significantly overexpressed in SMZL, including miR-21, miR-155 and miR-146a, whereas seven miRNAs showed significantly reduced expression, including miR-139, miR-345, miR-125a and miR-126. Furthermore, we identified miR-26b, a miRNA known to have tumor suppressive properties, as significantly downregulated in SMZL arising in HCV-positive patients (P0.0016). In conclusion, there is a characteristic dysregulation of miRNA expression in SMZL with a possible implication in its molecular tumorigenesis.

Original languageEnglish
Pages (from-to)1654-1662
Number of pages9
JournalLeukemia
Volume26
Issue number7
DOIs
Publication statusPublished - Jul 2012

Keywords

  • HCV
  • lymphoma
  • microRNA
  • miR-26b
  • splenic marginal zone lymphoma
  • virus

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

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