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Series GSE67113 Query DataSets for GSE67113
Status Public on Mar 20, 2016
Title MicroRNA-146a modulates B-cell oncogenesis by regulating EGR1
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary miR-146a is a NF-κB induced microRNA that serves as a feedback regulator of this critical pathway. In mice, deficiency of miR-146a results in hematolymphoid cancer at advanced ages as a consequence of constitutive NF-κB activity. In this study, we queried whether the deficiency of miR-146a contributes to B-cell oncogenesis. Combining miR-146a deficiency with transgenic expression of c-Myc led to the development of highly aggressive B-cell malignancies. Mice transgenic for c-Myc and deficient for miR-146a were characterized by significantly shortened survival, increased lymph node involvement, differential involvement of the spleen and a mature B-cell phenotype. High-throughput sequencing of the tumors revealed significant dysregulation of approximately 250 genes. Amongst these, the transcription factor Egr1 was consistently upregulated in mice deficient for miR-146a. Interestingly, transcriptional targets of Egr1 were enriched in both the high-throughput dataset and in a larger set of miR-146a-deficient tumors. miR-146a overexpression led to downregulation of Egr1 and downstream targets with concomitant decrease in cell growth. Direct targeting of the human EGR1 by miR-146a was seen by luciferase assay. Together our findings illuminate a bona fide role for miR-146a in the modulation of B-cell oncogenesis and reveal the importance of understanding microRNA function in a cell- and disease-specific context.
 
Overall design This experiment compares expression profiles between tumors that were derived from miR-146a +/+ and miR-146a-/- mice that are transgenic for c-Myc.
 
Contributor(s) Contreras JR, Palanichamy JK, Tran TM, Fernando TR, Rodriguez-Malave NI, Goswami N, Arboleda VA, Casero D, Rao D
Citation(s) 25906746
Submission date Mar 20, 2015
Last update date May 15, 2019
Contact name Dinesh S Rao
E-mail(s) drao@mednet.ucla.edu
Phone 3108251675
Organization name UCLA
Department PATHOLOGY AND LABORATORY MEDICINE
Street address 750 CHARLES E YOUNG DRIVE, 12-272 FACTOR
City LOS ANGELES
State/province CA
ZIP/Postal code 90095
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (6)
GSM1639213 Emu-Myc 146a+/+, sample 1
GSM1639214 Emu-Myc 146a+/+, sample 2
GSM1639215 Emu-Myc 146a+/+, sample 3
Relations
BioProject PRJNA278976
SRA SRP056377

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE67113_DineshRaoExpressionEstimates.txt.gz 834.8 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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