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| Status |
Public on Aug 31, 2012 |
| Title |
ADAR1 regulates melanoma progression via miRNAs biogenesis |
| Platform organisms |
Homo sapiens; synthetic construct |
| Sample organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Non-coding RNA profiling by array
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| Summary |
Aberrant RNA-editing was observed in several human tumors, but its significance is mostly unknown. Here we show that ADAR1, a ubiquitous RNA-editing enzyme, is commonly lost in metastatic melanoma cells and specimens. Experimental ADAR1 silencing significantly alters melanoma cell morphology, facilitates proliferation and cell-cycle, and increases the tumorigenicity in-vivo. A series of ADAR1 truncation mutants establishes a novel RNA-editing-independent role for ADAR1 in controlling the nuclear and cytoplasmic processing steps of miRNA biogenesis. Altered expression of ADAR1-controled miRNAs accounts for the observed phenotype. We show that the oncogenic miR-17-5p endogenously regulates ADAR1 expression and that its genomic sequence is frequently amplified in melanoma to overexpress the mature miR-17-5p form. ADAR1 and miR-17-5p are ubiquitously expressed, suggesting the generality of this mechanism.
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| Overall design |
Melanoma cell line expressing low ADAR1 levels (ADAR1-Knockdown) using shRNA technique were selected for RNA extraction and hybridization on Affymetrix microarrays. We sought to examine the alterations in the genes and microRNA expression profile in the manipulated cell system, due to ADAR1 possible involvement cancer development. To that end, we selected ADAR1-knockdown (ADAR1-KD) cells that demonstrated an enhanced aggressive phenotype both in vivo and in vitro as compared to the control cells (Control).
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| Contributor(s) |
Nemlich Y, Greenberg E, Ortenberg R, Besser MJ, Barshack I, Jacob-Hirsch J, Safran M, Prieto VG, Chakravarti N, Duncan L, Kallenberg DM, Bennett DC, Amariglio N, Bar-Eli M, Schachter J, Rechavi G, Markel G |
| Citation missing |
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| |
| Submission date |
Sep 07, 2011 |
| Last update date |
Oct 25, 2022 |
| Contact name |
jasmine Jacob |
| E-mail(s) |
j-jacob@sheba.health.gov.il
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| Phone |
0523790500
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| Organization name |
Sheba Medical Center at Tel HaShomer
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| Street address |
haChevel 33
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| City |
Shoham |
| State/province |
-Select- |
| ZIP/Postal code |
60850 |
| Country |
Israel |
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| Platforms (2) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
| GPL8786 |
[miRNA-1] Affymetrix Multispecies miRNA-1 Array |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA144993 |
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