Experiment Detail



Experiment IDEXP00110
ReferenceTitle: Myc-mediated repression of microRNA-34a promotes high-grade transformation ofB-cell lymphoma by dysregulation of FoxP1.
Author: Craig VJ, Cogliatti SB, Imig J, Renner C, Neuenschwander S, Rehrauer H,Schlapbach R, Dirnhofer S, Tzankov A, Müller A.
Journal: Blood. 2011 Jun 9;117(23):6227-36. doi: 10.1182/blood-2010-10-312231. Epub 2011Apr 1.
Abstract: Gastric marginal zone B-cell lymphoma of MALT type (MALT lymphoma) arises in the context of chronic inflammation induced by the bacterial pathogen Helicobacterpylori. Although generally considered an indolent disease, MALT lymphoma maytransform to gastric diffuse large B-cell lymphoma (gDLBCL) through mechanismsthat remain poorly understood. By comparing microRNA expression profiles ofgastric MALT lymphoma and gDLBCL, we have identified a signature of 27deregulated microRNAs(miRNAs) that share the characteristic of beingtranscriptionally repressed by Myc. Myc overexpression was consequently detected in 80% of gDLBCL but only 20% of MALT lymphomas spotted on a tissue microarray. Ahighly similar signature of Myc-repressed miRNAs was further detected in nodalDLBCL. Small interfering RNA-mediated knock-down of Myc blocked proliferation of DLBCL cell lines. Of the Myc-repressed miRNAs down-regulated in malignantlymphoma, miR-34a showed the strongest antiproliferative properties whenoverexpressed in DLBCL cells. We could further attribute miR-34a'stumor-suppressive effects to deregulation of its target FoxP1. FoxP1overexpression was detected in gDLBCL but not in gastric MALT lymphoma; FoxP1knock-down efficiently blocked DLBCL proliferation. In conclusion, our resultselucidate a novel Myc- and FoxP1-dependent pathway of malignant transformationand suggest miR-34a replacement therapy as a promising strategy in lymphomatreatment.
PMID: 21460242
Expressiion ProfileDescription: miRNA expression profile of human MALT lymphoma compared to gastritis and gDLBCL
Organism: Homo sapiens
GEO ID: GSE24485
Platform: GPL8227
Number of samples: 22
Design and SampleCancer Type: lymphoma
Cancer SubType: B cell lymphoma of MALT type
Cell Line: N/D
Experimental Design: high grade vs low grade
Case Sample: high grade MALT lymphoma
Control Sample: low grade MALT lhmphoma
Num of Case: 7
Num of Control: 8
Quantification Software: Limma
Num of miRNAs: 96
IdentificationNum of Up: 26
Num of Down: 25