Characterization of a set of tumor suppressor microRNAs in T cell acute lymphoblastic leukemia Journal Article

Authors: Sanghvi, V. R.; Mavrakis, K. J.; Van Der Meulen, J.; Boice, M.; Wolfe, A. L.; Carty, M.; Mohan, P.; Rondou, P.; Socci, N. D.; Benoit, Y.; Taghon, T.; Van Vlierberghe, P.; Leslie, C. S.; Speleman, F.; Wendel, H. G.
Article Title: Characterization of a set of tumor suppressor microRNAs in T cell acute lymphoblastic leukemia
Abstract: The posttranscriptional control of gene expression bymicroRNAs (miRNAs) is highly redundant, and compensatory effects limit the consequences of the inactivation of individual miRNAs. This implies that only a few miRNAs can function as effective tumor suppressors. It is also the basis of our strategy to define functionally relevant miRNA target genes that are not under redundant control by other miRNAs. We identified a functionally interconnected group of miRNAs that exhibited a reduced abundance in leukemia cells from patients with T cell acute lymphoblastic leukemia (T-ALL). To pinpoint relevant target genes, we applied a machine learning approach to eliminate genes that were subject to redundant miRNA-mediated control and to identify those genes that were exclusively targeted by tumor-suppressive miRNAs. This strategy revealed the convergence of a small group of tumor suppressor miRNAs on the Myb oncogene, as well as their effects on HBP1, which encodes a transcription factor. The expression of both genes was increased in T-ALL patient samples, and each gene promoted the progression of T-ALL in mice. Hence, our systematic analysis of tumor suppressor miRNA action identified a widespread mechanism of oncogene activation in T-ALL.
Keywords: functional assessment; human cell; nonhuman; cancer patient; animal cell; mouse; gene targeting; mus; microrna; gene expression; transcription factor; acute lymphoblastic leukemia; tumor suppressor gene; leukemia cell; oncogene c myc; thymocyte; oncogene myb; antiproliferative activity; lymphocyte subpopulation; machine learning; human; article
Journal Title: Science Signaling
Volume: 7
Issue: 352
ISSN: 1945-0877
Publisher: American Association for the Advancement of Science  
Date Published: 2014-11-18
Start Page: ra111
Language: English
DOI: 10.1126/scisignal.2005500
PROVIDER: scopus
PUBMED: 25406379
PMCID: PMC4693296
Notes: Export Date: 2 January 2015 -- Source: Scopus
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MSK Authors
  1. Nicholas D Socci
    188 Socci
  2. Hans Guido Wendel
    60 Wendel
  3. Christina Leslie
    112 Leslie
  4. Andrew Lerner Wolfe
    11 Wolfe
  5. Prathibha Mohan
    3 Mohan
  6. Michael   Boice
    5 Boice
  7. Mark Anthony Carty
    5 Carty