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GEO help: Mouse over screen elements for information. |
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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
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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.
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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.
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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
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Phone |
3108251675
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Organization name |
UCLA
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Department |
PATHOLOGY AND LABORATORY MEDICINE
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Street address |
750 CHARLES E YOUNG DRIVE, 12-272 FACTOR
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City |
LOS ANGELES |
State/province |
CA |
ZIP/Postal code |
90095 |
Country |
USA |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (6)
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Relations |
BioProject |
PRJNA278976 |
SRA |
SRP056377 |
Supplementary file |
Size |
Download |
File type/resource |
GSE67113_DineshRaoExpressionEstimates.txt.gz |
834.8 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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