| Title |
MicroRNA-378-mediated suppression of Runx1 alleviates the aggressive phenotype of triple-negative MDA-MB-231 human breast cancer cells
|
|---|---|
| Published in |
Tumor Biology, January 2016
|
| DOI | 10.1007/s13277-015-4710-6 |
| Pubmed ID | |
| Authors |
Gillian Browne, Julie A. Dragon, Deli Hong, Terri L. Messier, Jonathan A. R. Gordon, Nicholas H. Farina, Joseph R. Boyd, Jennifer J. VanOudenhove, Andrew W. Perez, Sayyed K. Zaidi, Janet L. Stein, Gary S. Stein, Jane B. Lian |
| Abstract |
The Runx1 transcription factor, known for its essential role in normal hematopoiesis, was reported in limited studies to be mutated or associated with human breast tumor tissues. Runx1 increases concomitantly with disease progression in the MMTV-PyMT transgenic mouse model of breast cancer. Compelling questions relate to mechanisms that regulate Runx1 expression in breast cancer. Here, we tested the hypothesis that dysregulation of Runx1-targeting microRNAs (miRNAs) allows for pathologic increase of Runx1 during breast cancer progression. Microarray profiling of the MMTV-PyMT model revealed significant downregulation of numerous miRNAs predicted to target Runx1. One of these, miR-378, was inversely correlated with Runx1 expression during breast cancer progression in mice and in human breast cancer cell lines MCF7 and triple-negative MDA-MB-231 that represent early- and late-stage diseases, respectively. MiR-378 is nearly absent in MDA-MB-231 cells. Luciferase reporter assays revealed that miR-378 binds the Runx1 3' untranslated region (3'UTR) and inhibits Runx1 expression. Functionally, we demonstrated that ectopic expression of miR-378 in MDA-MB-231 cells inhibited Runx1 and suppressed migration and invasion, while inhibition of miR-378 in MCF7 cells increased Runx1 levels and cell migration. Depletion of Runx1 in late-stage breast cancer cells resulted in increased expression of both the miR-378 host gene PPARGC1B and pre-miR-378, suggesting a feedback loop. Taken together, our study identifies a novel and clinically relevant mechanism for regulation of Runx1 in breast cancer that is mediated by a PPARGC1B-miR-378-Runx1 regulatory pathway. Our results highlight the translational potential of miRNA replacement therapy for inhibiting Runx1 in breast cancer. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 25% |
| Unknown | 3 | 75% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Scientists | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 26 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 23% |
| Student > Bachelor | 3 | 12% |
| Student > Doctoral Student | 2 | 8% |
| Other | 2 | 8% |
| Student > Master | 2 | 8% |
| Other | 5 | 19% |
| Unknown | 6 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 9 | 35% |
| Agricultural and Biological Sciences | 5 | 19% |
| Medicine and Dentistry | 3 | 12% |
| Psychology | 1 | 4% |
| Veterinary Science and Veterinary Medicine | 1 | 4% |
| Other | 0 | 0% |
| Unknown | 7 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 13 January 2016.
All research outputs
#13,437,318
of 23,655,983 outputs
Outputs from Tumor Biology
#874
of 2,614 outputs
Outputs of similar age
#184,116
of 397,366 outputs
Outputs of similar age from Tumor Biology
#45
of 282 outputs
Altmetric has tracked 23,655,983 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,614 research outputs from this source. They receive a mean Attention Score of 2.4. This one has gotten more attention than average, scoring higher than 66% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 397,366 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
We're also able to compare this research output to 282 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.