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

Viraj R. Sanghvi, Konstantinos J. Mavrakis, Joni Van Der Meulen, Michael Boice, Andrew L. Wolfe, Mark Carty, Prathibha Mohan, Pieter Rondou, Nicholas D. Socci, Yves Benoit, Tom Taghon, Pieter Van Vlierberghe, Christina S. Leslie, Frank Speleman, Hans Guido Wendel

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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.

Original languageEnglish (US)
Article numberra111
JournalScience Signaling
Volume7
Issue number352
DOIs
StatePublished - Nov 18 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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