| Literature DB >> 27300437 |
Silvia Nucera1, Alice Giustacchini2, Francesco Boccalatte2, Andrea Calabria1, Cristiana Fanciullo2, Tiziana Plati1, Anna Ranghetti1, Jose Garcia-Manteiga3, Davide Cittaro3, Fabrizio Benedicenti1, Eric R Lechman4, John E Dick4, Maurilio Ponzoni5, Fabio Ciceri6, Eugenio Montini1, Bernhard Gentner7, Luigi Naldini8.
Abstract
MicroRNA (miRNA)-126 is a known regulator of hematopoietic stem cell quiescence. We engineered murine hematopoiesis to express miRNA-126 across all differentiation stages. Thirty percent of mice developed monoclonal B cell leukemia, which was prevented or regressed when a tetracycline-repressible miRNA-126 cassette was switched off. Regression was accompanied by upregulation of cell-cycle regulators and B cell differentiation genes, and downregulation of oncogenic signaling pathways. Expression of dominant-negative p53 delayed blast clearance upon miRNA-126 switch-off, highlighting the relevance of p53 inhibition in miRNA-126 addiction. Forced miRNA-126 expression in mouse and human progenitors reduced p53 transcriptional activity through regulation of multiple p53-related targets. miRNA-126 is highly expressed in a subset of human B-ALL, and antagonizing miRNA-126 in ALL xenograft models triggered apoptosis and reduced disease burden.Entities:
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Year: 2016 PMID： 27300437 DOI： 10.1016/j.ccell.2016.05.007
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743