| Title |
Pleiotropic effects of miR-183~96~182 converge to regulate cell survival, proliferation and migration in medulloblastoma
|
|---|---|
| Published in |
Acta Neuropathologica, March 2012
|
| DOI | 10.1007/s00401-012-0969-5 |
| Pubmed ID | |
| Authors |
Shyamal Dilhan Weeraratne, Vladimir Amani, Natalia Teider, Jessica Pierre-Francois, Dominic Winter, Min Jeong Kye, Soma Sengupta, Tenley Archer, Marc Remke, Alfa H. C. Bai, Peter Warren, Stefan M. Pfister, Judith A. J. Steen, Scott L. Pomeroy, Yoon-Jae Cho |
| Abstract |
Medulloblastomas are the most common malignant brain tumors in children. Several large-scale genomic studies have detailed their heterogeneity, defining multiple subtypes with unique molecular profiles and clinical behavior. Increased expression of the miR-183~96~182 cluster of microRNAs has been noted in several subgroups, including the most clinically aggressive subgroup associated with genetic amplification of MYC. To understand the contribution of miR-183~96~182 to the pathogenesis of this aggressive subtype of medulloblastoma, we analyzed global gene expression and proteomic changes that occur upon modulation of miRNAs in this cluster individually and as a group in MYC-amplified medulloblastoma cells. Knockdown of the full miR-183~96~182 cluster results in enrichment of genes associated with apoptosis and dysregulation of the PI3K/AKT/mTOR signaling axis. Conversely, there is a relative enrichment of pathways associated with migration, metastasis and epithelial to mesenchymal transition, as well as pathways associated with dysfunction of DNA repair in cells with preserved miR-183 cluster expression. Immunocytochemistry and FACS analysis confirm induction of apoptosis upon knockdown of the miR-183 cluster. Importantly, cell-based migration and invasion assays verify the positive regulation of cell motility/migration by the miR-183 cluster, which is largely mediated by miR-182. We show that the effects on cell migration induced by the miR-183 cluster are coupled to the PI3K/AKT/mTOR pathway through differential regulation of AKT1 and AKT2 isoforms. Furthermore, we show that rapamycin inhibits cell motility/migration in medulloblastoma cells and phenocopies miR-183 cluster knockdown. Thus, the miR-183 cluster regulates multiple biological programs that converge to support the maintenance and metastatic potential of medulloblastoma. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Australia | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 106 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Australia | 1 | <1% |
| Sweden | 1 | <1% |
| Czechia | 1 | <1% |
| Canada | 1 | <1% |
| United States | 1 | <1% |
| Unknown | 101 | 95% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 32 | 30% |
| Researcher | 20 | 19% |
| Student > Master | 10 | 9% |
| Student > Bachelor | 7 | 7% |
| Professor > Associate Professor | 7 | 7% |
| Other | 16 | 15% |
| Unknown | 14 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 31 | 29% |
| Biochemistry, Genetics and Molecular Biology | 26 | 25% |
| Medicine and Dentistry | 19 | 18% |
| Neuroscience | 8 | 8% |
| Psychology | 3 | 3% |
| Other | 5 | 5% |
| Unknown | 14 | 13% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 August 2023.
All research outputs
#7,544,006
of 24,279,062 outputs
Outputs from Acta Neuropathologica
#1,409
of 2,470 outputs
Outputs of similar age
#48,240
of 159,907 outputs
Outputs of similar age from Acta Neuropathologica
#10
of 19 outputs
Altmetric has tracked 24,279,062 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 2,470 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.7. This one is in the 42nd percentile – i.e., 42% of its peers scored the same or lower than it.
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We're also able to compare this research output to 19 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.