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| Status |
Public on Dec 31, 2015 |
| Title |
ADAR1 regulates the resistance of melanoma cells to T cells via miR-222 and ICAM1 |
| Platform organism |
synthetic construct |
| Sample organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
The blossom of immunotherapy in melanoma highlights the need to delineate mechanisms of immune resistance. Recently, we have demonstrated that the RNA editing protein, adenosine deaminase acting on RNA-1 (ADAR1) is down-regulated during metastatic transition of melanoma, which enhances melanoma cell proliferation and tumorigenicity. Here we investigate the role of ADAR1 in melanoma immune resistance. Importantly, knockdown of ADAR1 in human melanoma cells induces resistance to tumor infiltrating lymphocytes in a cell contact-dependent mechanism. We show that ADAR1, in an editing-independent manner, regulates the biogenesis of miR-222 at the transcription level and thereby Intercellular Adhesion Molecule 1 (ICAM1) expression, which consequently affects melanoma immune resistance. ADAR1 thus has a novel, pivotal, role in cancer immune resistance. Corroborating with these results, the expression of miR-222 in melanoma tissue specimens was significantly higher in patients who had no clinical benefit from treatment with ipilimumab as compared to patients that responded clinically, suggesting that miR-222 could function as a biomarker for the prediction of response to ipilimumab. These results provide not only novel insights on melanoma immune resistance, but also pave the way to the development of innovative personalized tools to enable optimal drug selection and treatment.
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| Overall design |
13 formalin fixed paraffin embedded (FFPE) melanoma tissues were stained with hematoxilin and eosin for examination by an expert pathologist. Non-tumor tissue was removed. Total RNA was isolated using miRNeasy FFPE kit (Qiagen) according to the manufacture guidelines.
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| Contributor(s) |
Galore-Haskel G, Nemlich Y, Greenberg E, Ashkenazi S, Hakim M, Itzhaki O, Shoshani N, Shapira-Fromer R, Ben-Ami E, Ofek E, Anafi L, Besser MJ, Schachter J, Markel G |
| Citation(s) |
26338962 |
| Submission date |
Apr 01, 2015 |
| 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 (1) |
| GPL14613 |
[miRNA-2] Affymetrix Multispecies miRNA-2 Array |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA280087 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE67496_RAW.tar |
7.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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