microRNA 28 controls cell proliferation and is down-regulated in B-cell lymphomas Journal Article


Authors: Schneider, C.; Setty, M.; Holmes, A. B.; Maute, R. L.; Leslie, C. S.; Mussolin, L.; Rosolen, A.; Dalla-Favera, R.; Basso, K.
Article Title: microRNA 28 controls cell proliferation and is down-regulated in B-cell lymphomas
Abstract: Burkitt lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma (B-NHL), which originates from germinal center (GC) B cells and harbors translocations deregulating v-myc avian myelocytomatosis viral oncogene homolog (MYC). A comparative analysis of microRNAs expressed in normal and malignant GC B cells identified microRNA 28 (miR-28) as significantly down-regulated in BL, as well as in other GC-derived B-NHL. We show that reexpression of miR-28 impairs cell proliferation and clonogenic properties of BL cells by modulating several targets including MAD2 mitotic arrest deficient-like 1, MAD2L1, a component of the spindle checkpoint whose down-regulation is essential in mediating miR-28-induced proliferation arrest, and BCL2-associated athanogene, BAG1, an activator of the ERK pathway. We identify the oncogene MYC as a negative regulator of miR-28 expression, suggesting that its deregulation by chromosomal translocation in BL leads to miR-28 suppression. In addition, we show that miR-28 can inhibit MYC-induced transformation by directly targeting genes up-regulated by MYC. Overall, our data suggest that miR-28 acts as a tumor suppressor in BL and that its repression by MYC contributes to B-cell lymphomagenesis.
Keywords: signal transduction; controlled study; unclassified drug; human cell; nonhuman; comparative study; dna replication; cell proliferation; mouse; protein bcl 2; reverse transcription polymerase chain reaction; apoptosis; microrna; gene expression; animal experiment; animal model; protein; b cell lymphoma; germinal center; mitogen activated protein kinase 3; chromosome translocation; down regulation; large cell lymphoma; cell cycle regulation; follicular lymphoma; oncogene ras; short hairpin rna; burkitt lymphoma; oncogene myc; lymphoblastoid cell line; clonogenesis; rna sequence; protein mad2; mitosis inhibition; mad2l1 protein; m phase cell cycle checkpoint; human; priority journal; article; microrna 28; b-cell lymphoma cell line; raji cell line
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 111
Issue: 22
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2014-06-03
Start Page: 8185
End Page: 8190
Language: English
DOI: 10.1073/pnas.1322466111
PROVIDER: scopus
PMCID: PMC4050621
PUBMED: 24843176
DOI/URL:
Notes: Proc. Natl. Acad. Sci. U. S. A. -- Export Date: 8 July 2014 -- CODEN: PNASA -- Source: Scopus
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  1. Christina Leslie
    187 Leslie
  2. Manu Setty
    35 Setty