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| Status |
Public on Jan 09, 2008 |
| Title |
Alteration of microRNA gene expression by EBV encoded LMP1 oncogene |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
|
| Summary |
The Epstein Barr virus (EBV) encoded latent membrane protein-1 (LMP1) is a functional homologue of the tumor necrosis factor receptor family and contributes substantially to the oncogenic potential of EBV through activation of Nuclear Factor-kappaB (NF-kappaB). MicroRNAs (miRNAs) are a class of small RNA molecules that are involved in the regulation of cellular processes such as growth, development, and apoptosis, and have recently been linked to cancer phenotypes. Through miRNA microarray analysis, we demonstrate that LMP1 dysregulates the expression of several cellular miRNAs, including the most highly regulated of these, miR-146a. Quantitative RT-PCR analysis confirmed induced expression of miR-146a by LMP1. Analysis of miR-146a expression in EBV latency type III and type I cell lines revealed substantial expression of miR-146a in type III (which express LMP1) but not in type I cell lines. Reporter studies demonstrated that LMP1 induces miR-146a predominantly through two NF-kappaB binding sites in the miR-146a promoter and identified a role for an OCT-1 site in conferring basal and induced expression. Array analysis of cellular mRNAs expressed in Akata cells transduced with an miR-146a expressing retrovirus identified genes that are directly or indirectly regulated by miR-146a, including a group of interferon responsive genes that are inhibited by miR-146a. Since miR-146a is known to be induced by agents that activate the interferon response pathway (including LMP1), these results suggest that miR-146a functions in a negative feedback loop to modulate the intensity and/or duration of the interferon response.
Keywords: microRNA expression modified by EBV encoded oncogene, LMP1
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| Overall design |
EBV negative Mutu E1dn Cl. 3 cells were transduced with either a control retrovirus (pEhyg) or an LMP1 containing retrovirus (pEhyg-FLAG-LMP1). Cells were selected with hygromycin for approximately 2 weeks afterwhich 5 pairs of RNA preps were carried out on 5 successive days. Arrays GSM255656 and GSM255659 are dye swaps in which LMP1 samples were labeled with Cy3 and control samples were labeled with Cy5.
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| Contributor(s) |
Cameron JE, Yin Q, Fewell C, Lacey M, McBride J, Wang X, Lin Z, Schaefer BC, Flemington EK |
| Citation(s) |
18057241 |
| |
| Submission date |
Jan 08, 2008 |
| Last update date |
Mar 19, 2012 |
| Contact name |
Erik K Flemington |
| E-mail(s) |
[email protected]
|
| Phone |
504 988-1167
|
| Organization name |
Tulane Health Sciences Center
|
| Department |
Pathology
|
| Street address |
1430 Tulane Ave., SL79
|
| City |
New Orleans |
| State/province |
LA |
| ZIP/Postal code |
70112 |
| Country |
USA |
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| Platforms (1) |
| GPL6347 |
LC Sciences Human 4k microRNA array |
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| Samples (5)
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| GSM255655 |
microRNA expression in Cntl (Sample A) vs LMP1 (Sample B) transduced Mutu E1dn Cl. 3 cells - prep 1 |
| GSM255656 |
microRNA expression in LMP1 (Sample A) vs Cntl (Sample B) transduced Mutu E1dn Cl. 3 cells - prep 2 |
| GSM255658 |
microRNA expression in Cntl (Sample A) vs LMP1 (Sample B) transduced Mutu E1dn Cl. 3 cells - prep 3 |
| GSM255659 |
microRNA expression in LMP1 (Sample A) vs Cntl (Sample B) transduced Mutu E1dn Cl. 3 cells - prep 4 |
| GSM255660 |
microRNA expression in Cntl (Sample A) vs LMP1 (Sample B) transduced Mutu E1dn Cl. 3 cells - prep 5 |
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| This SubSeries is part of SuperSeries: |
| GSE10107 |
The EBV latent membrane protein 1 (LMP1) induces cellular microRNA-146a, a modulator of lymphocyte signaling pathways |
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| Relations |
| BioProject |
PRJNA108995 |
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