A Cooperative MicroRNA-tumor Suppressor Gene Network in Acute T-cell Lymphoblastic Leukemia (T-ALL)

Overview

Journal Nat Genet

Specialty Genetics

Date 2011 Jun 7

PMID 21642990

Citations 157

Authors

Konstantinos J Mavrakis

Joni Van der Meulen

Andrew L Wolfe

Xiaoping Liu

Evelien Mets

Tom Taghon

Aly A Khan

Manu Setty

Manu Setti

Pieter Rondou

Peter Vandenberghe

Eric Delabesse

Yves Benoit

Nicholas B Socci

Christina S Leslie

Pieter Van Vlierberghe

Frank Speleman

Hans-Guido Wendel

Affiliations

Soon will be listed here.

Abstract

The importance of individual microRNAs (miRNAs) has been established in specific cancers. However, a comprehensive analysis of the contribution of miRNAs to the pathogenesis of any specific cancer is lacking. Here we show that in T-cell acute lymphoblastic leukemia (T-ALL), a small set of miRNAs is responsible for the cooperative suppression of several tumor suppressor genes. Cross-comparison of miRNA expression profiles in human T-ALL with the results of an unbiased miRNA library screen allowed us to identify five miRNAs (miR-19b, miR-20a, miR-26a, miR-92 and miR-223) that are capable of promoting T-ALL development in a mouse model and which account for the majority of miRNA expression in human T-ALL. Moreover, these miRNAs produce overlapping and cooperative effects on tumor suppressor genes implicated in the pathogenesis of T-ALL, including IKAROS (also known as IKZF1), PTEN, BIM, PHF6, NF1 and FBXW7. Thus, a comprehensive and unbiased analysis of miRNA action in T-ALL reveals a striking pattern of miRNA-tumor suppressor gene interactions in this cancer.

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