Author/Authors :
Anna M. Eiring، نويسنده , , Jason G. Harb، نويسنده , , Paolo Neviani، نويسنده , , Christopher Garton، نويسنده , , Joshua J. Oaks، نويسنده , , Riccardo Spizzo، نويسنده , , Shujun Liu، نويسنده , , Sebastian Schwind، نويسنده , , Ramasamy Santhanam، نويسنده , , Christopher J. Hickey، نويسنده , , Heiko Becker، نويسنده , , Jason C. Chandler، نويسنده , , Raul Andino، نويسنده , , Jorge Cortes، نويسنده , , Peter Hokland، نويسنده , , Claudia S. Huettner، نويسنده , , Ravi Bhatia، نويسنده , , Denis C. Roy، نويسنده , , Stephen A. Liebhaber، نويسنده , , Michael A. Caligiuri، نويسنده , , et al.، نويسنده ,
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 microRNAʹs 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.
