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Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8185-90. doi: 10.1073/pnas.1322466111. Epub 2014 May 19.

MicroRNA 28 controls cell proliferation and is down-regulated in B-cell lymphomas.

Author information

1
Institute for Cancer Genetics.
2
Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065;
3
Clinica di Oncoematologia Pediatrica, Azienda Ospedaliera-Università di Padova, 35128 Padua, Italy; andIstituto di Ricerca Pediatrico Fondazione Città della Speranza, 35127 Padua, Italy.
4
Clinica di Oncoematologia Pediatrica, Azienda Ospedaliera-Università di Padova, 35128 Padua, Italy; and.
5
Institute for Cancer Genetics,Herbert Irving Comprehensive Cancer Center, andDepartments of Pathology and Cell Biology,Genetics and Development, andMicrobiology and Immunology, Columbia University, New York, NY 10032;
6
Institute for Cancer Genetics,Departments of Pathology and Cell Biology, kb451@columbia.edu.

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.

PMID:
24843176
PMCID:
PMC4050621
DOI:
10.1073/pnas.1322466111
[Indexed for MEDLINE]
Free PMC Article

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