title: Overexpression of microRNAs from the miR-17-92 paralog clusters in AIDS-related non-Hodgkin's lymphomas.
abstract: BACKGROUND
  Individuals infected by HIV are at an increased risk for developing non-Hodgkin's lymphomas (AIDS-NHL). In the highly active antiretroviral therapy (HAART) era, there has been a significant decline in the incidence of AIDS-associated primary central nervous system lymphoma (PCNSL). However, only a modest decrease in incidence has been reported for other AIDS-NHL subtypes. Thus, AIDS-NHLs remain a significant cause of morbidity and mortality in HIV infected individuals. Recently, much attention has been directed toward the role of miRNAs in cancer, including NHL. Several miRNAs, including those encoded by the miR-17-92 polycistron, have been shown to play significant roles in B cell tumorigenesis. However, the role of miRNAs in NHL in the setting of HIV infection has not been defined.
  
  
  RESULTS
  We used quantitative realtime PCR to assess the expression of miRNAs from three different paralog clusters, miR-17-92, miR-106a-363, and miR-106b-25 in 24 cases of AIDS-NHLs representing four tumor types, Burkitt's lymphoma (BL, n = 6), diffuse large B-cell lymphoma (DLBCL, n = 8), primary central nervous system lymphoma (PCNSL, n = 5), and primary effusion lymphoma (PEL, n = 5). We also used microarray analysis to identify a differentiation specific miRNA signature of naïve, germinal center, and memory B cell subsets from tonsils (n = 4). miRNAs from the miR-17-92 paralog clusters were upregulated by B cells, specifically during the GC differentiation stage. We also found overexpression of these miRNA clusters in all four AIDS-NHL subtypes. Finally, we also show that select miRNAs from these clusters (miR-17, miR-106a, and miR-106b) inhibited p21 in AIDS-BL and DLBCL cases, thus providing a mechanistic role for these miRNAs in AIDS-NHL pathogenesis.
  
  
  CONCLUSIONS
  Dysregulation of miR-17-92 paralog clusters is a common feature of AIDS-associated NHLs.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Dharma R
authors.initials: DR
authors.lastname: Thapa
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.forename: Beth D
authors.initials: BD
authors.lastname: Jamieson
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martínez-Maza
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D005810:Multigene Family; D012323:RNA Processing, Post-Transcriptional
chemical_list: D017931:DNA Primers; D035683:MicroRNAs