Differentiation stage-specific expression of microRNAs in B lymphocytes and diffuse large B-cell lymphomas

Raquel Malumbres, Kristopher A. Sarosiek, Elena Cubedo, Jose W. Ruiz, Xiaoyu Jiang, Randy D. Gascoyne, Robert Tibshirani, Izidore S. Lossos

Research output: Contribution to journalArticle

202 Scopus citations

Abstract

miRNAs are small RNA molecules binding to partially complementary sites in the 3′-UTR of target transcripts and repressing their expression. miRNAs orchestrate multiple cellular functions and play critical roles in cell differentiation and cancer development. We analyzed miRNA profiles in B-cell subsets during peripheral B-cell differentiation as well as in diffuse large B-cell lymphoma (DLBCL) cells. Our results show temporal changes in the miRNA expression during B-cell differentiation with a highly unique miRNA profile in germinal center (GC) lymphocytes. We provide experimental evidence that these changes may be physiologically relevant by demonstrating that GC-enriched hsa-miR-125b down-regulates the expression of IRF4 and PRDM1/BLIMP1, and memory B cell-enriched hsa-miR-223 down-regulates the expression of LMO2. We further demonstrate that although an important component of the biology of a malignant cell is inherited from its nontransformed cellular progenitor - GC centroblasts - aberrant miRNA expression is acquired upon cell transformation. A 9-miRNA signature was identified that could precisely differentiate the 2 major subtypes of DLBCL. Finally, expression of some of the miRNAs in this signature is correlated with clinical outcome of uniformly treated DLBCL patients.

Original languageEnglish (US)
Pages (from-to)3754-3764
Number of pages11
JournalBlood
Volume113
Issue number16
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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