title: A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL).
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.
authors.affiliation: Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Konstantinos J
authors.initials: KJ
authors.lastname: Mavrakis
authors.forename: Joni
authors.initials: J
authors.lastname: Van Der Meulen
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Wolfe
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.forename: Evelien
authors.initials: E
authors.lastname: Mets
authors.forename: Tom
authors.initials: T
authors.lastname: Taghon
authors.forename: Aly A
authors.initials: AA
authors.lastname: Khan
authors.forename: Manu
authors.initials: M
authors.lastname: Setty
authors.forename: Manu
authors.initials: M
authors.lastname: Setti
authors.forename: Pieter
authors.initials: P
authors.lastname: Rondou
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenberghe
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
authors.forename: Yves
authors.initials: Y
authors.lastname: Benoit
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Socci
authors.forename: Christina S
authors.initials: CS
authors.lastname: Leslie
authors.forename: Pieter
authors.initials: P
authors.lastname: Van Vlierberghe
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.forename: Hans-Guido
authors.initials: HG
authors.lastname: Wendel
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger; D008156:Luciferases