|
| Status |
Public on Jun 26, 2018 |
| Title |
MiR-34a controls proliferation and plasticity of early-progenitors in the normal mammary gland and in breast cancer |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The miR-34 is a tumor-suppressor miRNA family involved in various human cancers, including breast. However, the role of such miRNAs in the control of mammary stem cells (MaSCs), early-progenitors and their tumor counterparts, (CSCs) lies largely unexplored. Here, we identified miR-34a as directly regulated by TP53 in primary mouse mammospheres. Expression of miR-34a is induced upon luminal commitment and differentiation and able to inhibit the expansion of the MaSCs/early-progenitor pool in a p53-independent fashion. Loss of function approaches revealed that miR-34 negatively controls both proliferation and fate commitment in mammary progenitors by modulating several pathways involved in epithelial cell plasticity and luminal-to-basal conversion. In particular, miR-34a negatively regulates Wnt/b-catenin signaling pathway, targeting multiple upstream regulators and, thus, modulating the expansion of the MaSCs/early-progenitor pool. These multiple roles of miR-34a were maintained in a model of human breast cancer, where chronic expression of miR-34a in triple-negative mesenchymal-like cells (enriched in CSCs) reduced tumor growth, restricted CSC pool and inhibited tumor propagation by promoting a luminal-like differentiation program.
|
| |
|
| Overall design |
gene expression by deep-sequencing in mammary epithelial undifferentiated Sca high cells, differentiatied Sca low cells and in Sca high cells upon miR-34a induction. Each sample is analyzed in triplicate
|
| |
|
| Contributor(s) |
Bonetti P, Marzi MJ, Nicassio F |
| Citation(s) |
30093634 |
| |
| Submission date |
May 30, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Francesco Nicassio |
| E-mail(s) |
francesco.nicassio@iit.it
|
| Organization name |
Istituto Italiano di Tecnologia
|
| Department |
Center for genomic science
|
| Street address |
Via Adamello 16
|
| City |
Milano |
| ZIP/Postal code |
20139 |
| Country |
Italy |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA388393 |
| SRA |
SRP108253 |
Less...
More...