Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA309420 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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.
2014-02-18 | GSE39983 | GEO
Project description:Malignant melanoma is the most aggressive form of skin cancer therefore it is crucial to disclose its underlying molecular mechanisms. MicroRNAs are small endogenous non-coding RNAs able to post-transcriptionally down-regulate the expression of direct target genes. Using a melanoma progression model, we identified miR-146a as a key double-acting player in melanoma malignancy. In fact, miR-146a is able to enhance tumor growth while it suppresses dissemination. We evidenced that melanoma cell growth is coordinated by its direct target lunatic fringe (LFNG) which operates on the NOTCH/PTEN/Akt pathway. Instead, metastasis formation inhibition is linked to decreased expression of ITGAV and ROCK1. Relevantly, miR-146a expression correlates with melanoma recurrence and it is enriched both in patients-derived melanoma and cutaneous metastasis samples, while its direct targets are depleted. However, miR-146a levels drop in Circulating Tumor Cells, suggesting the necessity for miR-146a expression to fluctuate during tumor progression in order to favor tumor growth and allow dissemination. This study reconciles the contradictory biological functions of miR-146a in melanoma progression and unravels distinct molecular mechanisms that need to be considered for therapeutic interventions.
2016-03-18 | GSE77090 | GEO
Project description: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. 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.
2014-02-18 | E-GEOD-39294 | biostudies-arrayexpress
Project description: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.
2014-02-18 | GSE39294 | GEO
Project description: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. WI-38 cells were either infected with BRAFV600E or Empty retroviral vectors and small RNA were prepared from these cells. As an additional control, WI-38 cells were serum starved and used to generate quiscent cells, which were also used to prepase small RNA. The small RNA were then used to generate small RNA library and were used on Illumina genome analyzer.
2014-02-18 | E-GEOD-39983 | biostudies-arrayexpress
Project description:miR-146a promotes the initiation and progression of melanoma by activating Notch signaling
| PRJNA170508 | ENA
Project description:miR-146a promotes the initiation and progression of melanoma by activating Notch signaling
| PRJNA172202 | ENA
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO
Project description:miR-146a is a NF-κB induced microRNA that serves as a feedback regulator of this critical pathway. In mice, deficiency of miR-146a results in hematolymphoid cancer at advanced ages as a consequence of constitutive NF-κB activity. In this study, we queried whether the deficiency of miR-146a contributes to B-cell oncogenesis. Combining miR-146a deficiency with transgenic expression of c-Myc led to the development of highly aggressive B-cell malignancies. Mice transgenic for c-Myc and deficient for miR-146a were characterized by significantly shortened survival, increased lymph node involvement, differential involvement of the spleen and a mature B-cell phenotype. High-throughput sequencing of the tumors revealed significant dysregulation of approximately 250 genes. Amongst these, the transcription factor Egr1 was consistently upregulated in mice deficient for miR-146a. Interestingly, transcriptional targets of Egr1 were enriched in both the high-throughput dataset and in a larger set of miR-146a-deficient tumors. miR-146a overexpression led to downregulation of Egr1 and downstream targets with concomitant decrease in cell growth. Direct targeting of the human EGR1 by miR-146a was seen by luciferase assay. Together our findings illuminate a bona fide role for miR-146a in the modulation of B-cell oncogenesis and reveal the importance of understanding microRNA function in a cell- and disease-specific context.
2016-03-20 | GSE67113 | GEO
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
2011-08-25 | GSE23936 | GEO