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Status |
Public on Aug 09, 2016 |
Title |
Expression profiling of fibroblasts treated with miR-211 and miR-320c |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
mRNA profiles generated from primary fibroblast upon treatment with miR-211, miR-302 or melanoma melanosomes. Abstract: Melanoma originates in the epidermis and enters the metastatic and lethal phase upon invasion into the dermis. However, the interactions between melanoma cells and the dermis prior to this invasion have been poorly studied. Here we uncover that melanoma cells directly affect the formation of the dermal tumor niche by microRNA (miRNA) trafficking prior to invading the dermis. Melanocytes, the cells of melanoma origin, are specialized in trafficking of pigment vesicles, termed melanosomes and, interestingly, melanoma cells retain this trafficking ability. In melanoma in-situ specimens, we found melanosome markers in distal fibroblasts prior to the invasion of melanoma cells into the dermis. Melanoma-derived melanosomes carry miRNAs into primary fibroblasts that trigger changes in the fibroblasts, including increased proliferation, migration, and expression of pro-inflammatory genes, all known features of cancer-associated fibroblasts (CAFs). Specifically, we found that melanosomal miRNA-211 directly targets IGF2R and leads to MAPK signaling activation in fibroblasts, which reciprocally encourages melanoma growth. Treatment of melanoma cells with a melanosome release-inhibitor prevented CAF formation. Since the first interaction of melanoma cells with blood vessels occurs in the dermis, our data suggest a promising opportunity to block melanoma cell invasion by preventing the formation of the dermal tumor niche. In the paper we showed the 10% of most differentially expressed mRNA upon miR-211, miR-320c and melanosomes treatment and overlap of 2000 downregulated mRNA upon miR-211 and melanosomes treatment with predicted target gene miR-211 and CAFs related genes
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Overall design |
Expresssion profiling was performed for primary fibroblasts transfected with miRNA-211 mimic and miRNA-320c mimic.
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Contributor(s) |
Levy C, Dror S, Hoheisel JD, Sander L |
Citation missing |
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Submission date |
Sep 01, 2015 |
Last update date |
Aug 11, 2016 |
Contact name |
Carmit Levy |
E-mail(s) |
carmitlevy@post.tau.ac.il
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Organization name |
Tel Aviv University
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Department |
Human Genetics and Biochemistry
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Lab |
Sackler School of Medicine
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Street address |
Ramat Aviv
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City |
Tel Aviv |
ZIP/Postal code |
69978 |
Country |
Israel |
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Platforms (1) |
GPL20880 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [HuGene11st_Hs_ENTREZG_18.0.0] |
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Samples (8)
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This SubSeries is part of SuperSeries: |
GSE72620 |
Melanoma miRNA trafficking triggers the tumor primary niche formation |
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Relations |
BioProject |
PRJNA294465 |