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| Status |
Public on Feb 18, 2014 |
| Title |
miR-146a promotes the initiation and progression of melanoma by activating Notch signaling |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Oncogenic mutations in BRAF and NRAS occur in 70% of melanomas. Here we identify a microRNA, miR-146a, that is highly upregulated by oncogenic BRAF and NRAS. Expression of miR-146a increases the ability of human melanoma cells to proliferate in culture and form tumors in mice, whereas knockdown of miR-146a has the opposite effects. We show these oncogenic activities are due to miR-146a targeting the NUMB mRNA, a repressor of Notch signaling. Previous studies have shown that pre-miR-146a contains a single nucleotide polymorphism (C>G rs2910164). We find that the ability of pre-miR-146a/G to activate Notch signaling and promote oncogenesis is substantially higher than that of pre-miR-146a/C. Analysis of melanoma cell lines and matched patient samples indicates that during melanoma progression pre-miR-146a/G is enriched relative to pre-miR-146a/C, resulting from a C-to-G somatic mutation in pre-miR-146a/C. Collectively, our results reveal a central role for miR-146a in the initiation and progression of melanoma.
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| Overall design |
SKMEL28 melanoma cell line stably expressing either an empty vector or pre-miR146a with either C or G SNP (SKMEL28-FG12, SKMEL28-miR-146a/C and SKMEL28-miR-146a/G) were used to prepare total RNA. Microarray analysis was performed by using biological replicates for each stable cell lines for a total of 6 samples.
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| Contributor(s) |
Forloni M, Dogra S, Dong Y, Conte D, Zhu JL, Ou J, Deng A, Mahalingam M, Green MR, Wajapeyee N |
| Citation(s) |
24550252 |
| Submission date |
Jul 12, 2012 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Narendra Wajapeyee |
| E-mail(s) |
nwajapey@uab.edu
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| Phone |
205-934-5331
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| Organization name |
University of Alabama at Birmingham
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| Department |
Department of Biochemistry and Molecular Genetics
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| Street address |
720 20th Street South, Kaul 540A
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| City |
Birmingham |
| State/province |
AL |
| ZIP/Postal code |
35233 |
| Country |
USA |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA170508 |
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