miR-328 Functions as an RNA Decoy to Modulate hnRNP E2 Regulation of mRNA Translation in Leukemic Blasts

被引：440

作者：

Eiring, Anna M. ^{[1
]}

Harb, Jason G. ^{[1
]}

Neviani, Paolo ^{[1
]}

Garton, Christopher ^{[1
]}

Oaks, Joshua J. ^{[1
]}

Spizzo, Riccardo ^{[6
,7
]}

Liu, Shujun ^{[2
]}

Schwind, Sebastian ^{[2
,3
]}

Santhanam, Ramasamy ^{[1
]}

Hickey, Christopher J. ^{[2
,3
]}

Becker, Heiko ^{[2
,3
]}

Chandler, Jason C. ^{[2
]}

Andino, Raul ^{[5
]}

Cortes, Jorge ^{[6
,7
]}

Hokland, Peter ^{[8
]}

Huettner, Claudia S. ^{[9
]}

Bhatia, Ravi ^{[10
]}

Roy, Denis C. ^{[11
,12
]}

Liebhaber, Stephen A. ^{[13
]}

Caligiuri, Michael A. ^{[1
,2
,3
]}

Marcucci, Guido ^{[1
,2
,3
]}

Garzon, Ramiro ^{[1
,2
,3
]}

Croce, Carlo M. ^{[1
,3
]}

Calin, George A. ^{[6
,7
]}

Perrotti, Danilo ^{[1
,3
,4
]}

机构：

[1] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Human Canc Genet Program, Columbus, OH 43210 USA

[2] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA

[3] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA

[4] Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA

[5] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA

[6] Univ Texas Houston, MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNAs, Dept Leukemia, Houston, TX 77030 USA

[7] Univ Texas Houston, MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNAs, Dept Expt Therapeut, Houston, TX 77030 USA

[8] Aarhus Univ, Dept Hematol, DK-8000 Aarhus C, Denmark

[9] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA

[10] City Hope Natl Med Ctr, Dept Hematopoiet Stem Cell & Leukemia Res, Duarte, CA 91010 USA

[11] Hop Maison Neuve Rosemont, Dept Hematol Oncol, Montreal, PQ H3T 1J4, Canada

[12] Univ Montreal, Montreal, PQ H3T 1J4, Canada

[13] Univ Penn, Sch Med, Dept Genet & Med, Philadelphia, PA 19104 USA

来源：

CELL | 2010年 / 140卷 / 05期

关键词：

CHRONIC MYELOID-LEUKEMIA; C/EBP-ALPHA; CD34(+) CELLS; BCR/ABL; BINDING; IDENTIFICATION; EXPRESSION; MICRORNAS; TARGETS; MYELOPEROXIDASE;

D O I：

10.1016/j.cell.2010.01.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：652 / 665

页数：14

共 45 条

[1] Down-Regulation of hsa-miR-10a in Chronic Myeloid Leukemia CD34+ Cells Increases USF2-Mediated Cell Growth [J].

Agirre, Xabier ;

Jimenez-Velasco, Antonio ;

San Jose-Eneriz, Edurne ;

Garate, Leire ;

Bandres, Eva ;

Cordeu, Lucia ;

Aparicio, Oscar ;

Saez, Borja ;

Navarro, German ;

Vilas-Zornoza, Amaia ;

Perez-Roger, Ignacio ;

Garcia-Foncillas, Jesus ;

Torres, Antonio ;

Heiniger, Anabel ;

Jose Calasanz, Maria ;

Fortes, Puri ;

Roman-Gomez, Jose ;

Prosper, Felipe .

MOLECULAR CANCER RESEARCH, 2008, 6 (12) :1830-1840

[2] MicroRNAs: Target Recognition and Regulatory Functions [J].

Bartel, David P. .

CELL, 2009, 136 (02) :215-233

[3] Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome [J].

Brown, V ;

Jin, P ;

Ceman, S ;

Darnell, JC ;

O'Donnell, WT ;

Tenenbaum, SA ;

Jin, XK ;

Feng, Y ;

Wilkinson, KD ;

Keene, JD ;

Darnell, RB ;

Warren, ST .

CELL, 2001, 107 (04) :477-487

[4] Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression [J].

Bueno, Maria J. ;

Perez de Castro, Ignacio ;

de Cedron, Marta Gomez ;

Santos, Javier ;

Calin, George A. ;

Cigudosa, Juan C. ;

Croce, Carlo M. ;

Fernandez-Piqueras, Jose ;

Malumbres, Marcos .

CANCER CELL, 2008, 13 (06) :496-506

[5] The roles of heterogeneous nuclear ribonucleoproteins in tumour development and progression [J].

Carpenter, Bnian ;

MacKay, Catriona ;

Alnabulsi, Ayham ;

MacKay, Morven ;

Telfer, Colin ;

Melvin, William T. ;

Murray, Graeme I. .

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2006, 1765 (02) :85-100

[6] High levels of the BCR/ABL oncoprotein are required for the MAPK-hnRNP-E2-dependent suppression of C/EBPα-driven myeloid differentiation [J].

Chang, Ii Suk ;

Santhanam, Ramasamy ;

Trotta, Rossana ;

Neviani, Paolo ;

Eiring, Anna M. ;

Briercheck, Edward ;

Ronchetti, Mattia ;

Roy, Denis C. ;

Calabretta, Bruno ;

Caligiuri, Michael A. ;

Perrotti, Danilo .

BLOOD, 2007, 110 (03) :994-1003

[7] MicroRNAs modulate hematopoietic lineage differentiation [J].

Chen, CZ ;

Li, L ;

Lodish, HF ;

Bartel, DP .

SCIENCE, 2004, 303 (5654) :83-86

[8] TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing [J].

Chendrimada, TP ;

Gregory, RI ;

Kumaraswamy, E ;

Norman, J ;

Cooch, N ;

Nishikura, K ;

Shiekhattar, R .

NATURE, 2005, 436 (7051) :740-744

[9] Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function [J].

Darnell, JC ;

Jensen, KB ;

Jin, P ;

Brown, V ;

Warren, ST ;

Darnell, RB .

CELL, 2001, 107 (04) :489-499

[10] Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis [J].

Eiring, Anna M. ;

Neviani, Paolo ;

Santhanam, Ramasamy ;

Oaks, Joshua J. ;

Chang, Ji Suk ;

Notari, Mario ;

Willis, William ;

Gambacorti-Passerini, Carlo ;

Volinia, Stefano ;

Marcucci, Guido ;

Caligiuri, Michael A. ;

Leone, Gustavo W. ;

Perrotti, Danilo .

BLOOD, 2008, 111 (02) :816-828

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