| Title |
MicroRNA profiling of the pubertal mouse mammary gland identifies miR-184 as a candidate breast tumour suppressor gene
|
|---|---|
| Published in |
Breast Cancer Research, June 2015
|
| DOI | 10.1186/s13058-015-0593-0 |
| Pubmed ID | |
| Authors |
Yu Wei Phua, Akira Nguyen, Daniel L. Roden, Benjamin Elsworth, Niantao Deng, Iva Nikolic, Jessica Yang, Andrea Mcfarland, Roslin Russell, Warren Kaplan, Mark J. Cowley, Radhika Nair, Elena Zotenko, Sandra O’Toole, Shi-xiong Tan, David E. James, Susan J. Clark, Hosein Kouros-Mehr, Alexander Swarbrick |
| Abstract |
The study of mammalian development has offered many insights into the molecular aetiology of cancer. We previously used analysis of mammary morphogenesis to discover a critical role for GATA-3 in mammary developmental and carcinogenesis. In recent years an important role for microRNAs (miRNAs) in a myriad of cellular processes in development and in oncogenesis has emerged. microRNA profiling was conducted on stromal and epithelial cellular subsets microdissected from the pubertal mouse mammary gland. miR-184 was reactivated by transient or stable overexpression in breast cancer cell lines and examined using a series of in vitro (proliferation, tumour-sphere and protein synthesis) assays. Orthotopic xenografts of breast cancer cells were used to assess the effect of miR-184 on tumourigenesis as well as distant metastasis. Interactions between miR-184 and its putative targets were assessed by quantitative PCR, microarray, bioinformatics and 3' untranslated region Luciferase reporter assay. The methylation status of primary patient samples was determined by MBD-Cap sequencing. Lastly, the clinical prognostic significance of miR-184 putative targets was assessed using publicly available datasets. A large number of microRNA were restricted in their expression to specific tissue subsets. MicroRNA-184 (miR-184) was exclusively expressed in epithelial cells and markedly upregulated during differentiation of the proliferative, invasive cells of the pubertal terminal end bud (TEB) into ductal epithelial cells in vivo. miR-184 expression was silenced in mouse tumour models compared to non-transformed epithelium and in a majority of breast cancer cell line models. Ectopic reactivation of miR-184 inhibited the proliferation and self-renewal of triple negative breast cancer (TNBC) cell lines in vitro and delayed primary tumour formation and reduced metastatic burden in vivo. Gene expression studies uncovered multi-factorial regulation of genes in the AKT/mTORC1 pathway by miR-184. In clinical breast cancer tissues, expression of miR-184 is lost in primary TNBCs while the miR-184 promoter is methylated in a subset of lymph node metastases from TNBC patients. These studies elucidate a new layer of regulation in the PI3K/AKT/mTOR pathway with relevance to mammary development and tumour progression and identify miR-184 as a putative breast tumour suppressor. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Practitioners (doctors, other healthcare professionals) | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 50 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 11 | 22% |
| Student > Ph. D. Student | 10 | 20% |
| Student > Master | 6 | 12% |
| Student > Bachelor | 5 | 10% |
| Other | 4 | 8% |
| Other | 4 | 8% |
| Unknown | 10 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 13 | 26% |
| Biochemistry, Genetics and Molecular Biology | 10 | 20% |
| Medicine and Dentistry | 5 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 8% |
| Psychology | 2 | 4% |
| Other | 5 | 10% |
| Unknown | 11 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 June 2015.
All research outputs
#17,285,668
of 25,374,647 outputs
Outputs from Breast Cancer Research
#1,535
of 2,052 outputs
Outputs of similar age
#166,037
of 278,332 outputs
Outputs of similar age from Breast Cancer Research
#28
of 36 outputs
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