title: miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts.
abstract: MicroRNAs and heterogeneous ribonucleoproteins (hnRNPs) are posttranscriptional gene regulators that bind mRNA in a sequence-specific manner. Here, we report that loss of miR-328 occurs in blast crisis chronic myelogenous leukemia (CML-BC) in a BCR/ABL dose- and kinase-dependent manner through the MAPK-hnRNP E2 pathway. Restoration of miR-328 expression rescues differentiation and impairs survival of leukemic blasts by simultaneously interacting with the translational regulator poly(rC)-binding protein hnRNP E2 and with the mRNA encoding the survival factor PIM1, respectively. The interaction with hnRNP E2 is independent of the microRNA's seed sequence and it leads to release of CEBPA mRNA from hnRNP E2-mediated translational inhibition. Altogether, these data reveal the dual ability of a microRNA to control cell fate both through base pairing with mRNA targets and through a decoy activity that interferes with the function of regulatory proteins.
authors.affiliation: Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Eiring
authors.forename: Jason G
authors.initials: JG
authors.lastname: Harb
authors.forename: Paolo
authors.initials: P
authors.lastname: Neviani
authors.forename: Christopher
authors.initials: C
authors.lastname: Garton
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Oaks
authors.forename: Riccardo
authors.initials: R
authors.lastname: Spizzo
authors.forename: Shujun
authors.initials: S
authors.lastname: Liu
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schwind
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Santhanam
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hickey
authors.forename: Heiko
authors.initials: H
authors.lastname: Becker
authors.forename: Jason C
authors.initials: JC
authors.lastname: Chandler
authors.forename: Raul
authors.initials: R
authors.lastname: Andino
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Peter
authors.initials: P
authors.lastname: Hokland
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Huettner
authors.forename: Ravi
authors.initials: R
authors.lastname: Bhatia
authors.forename: Denis C
authors.initials: DC
authors.lastname: Roy
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Liebhaber
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Ramiro
authors.initials: R
authors.lastname: Garzon
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.forename: Danilo
authors.initials: D
authors.lastname: Perrotti
mesh_terms: D000818:Animals; D001752:Blast Crisis; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000378:metabolism
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C548170:MIRN328 microRNA, human; C548169:MIRN328 microRNA, mouse; D035683:MicroRNAs; D034743:RNA-Induced Silencing Complex; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1