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| Status |
Public on Jul 06, 2020 |
| Title |
Expression of ncRNAs on the DLK1-DIO3 locus is associated with basel and mesenchymal phenotype in breast epithelial progenitor cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Epithelial-to-mesenchymal transition (EMT) and its reversed process mesenchymal-to-epithelial transition (MET) play a critical role in epithelial plasticity during development and cancer progression. Among important regulators of these cellular processes are non-coding RNAs (ncRNAs). The imprinted DLK1-DIO3 locus, containing numerous maternally expressed ncRNAs including the lncRNA maternally expressed gene 3 (MEG3) and a cluster of over 50 miRNAs, has been shown to be a modulator of stemness in embryonic stem cells and in cancer progression, potentially through the tumor suppressor role of MEG3. In this study we analyzed the expression pattern and functional role of ncRNAs from the DLK1-DIO3 locus in epithelial plasticity of the breast. We studied their expression in various cell types of breast tissue and revisit the role of the locus in EMT/MET using a breast epithelial progenitor cell line (D492) and its isogenic mesenchymal derivative (D492M). Marked upregulation of ncRNAs from the DLK1-DIO3 locus was seen after EMT induction in two cell line models of EMT. In addition, the expression of MEG3 and the maternally expressed ncRNAs was higher in stromal cells compared to epithelial cell types in primary breast tissue. We also show that expression of MEG3 is concomitant with the expression of the ncRNAs from the DLK1-DIO3 locus and its expression is therefore likely indicative of activation of all ncRNAs at the locus. MEG3 expression is correlated with stromal markers in normal tissue and breast cancer tissue and negatively correlated with the survival of breast cancer patients in two different cohorts. Overexpression of MEG3 using CRISPR activation in a breast epithelial cell line induced partial EMT and enriched for a basal-like phenotype. Conversely, knock down of MEG3 using CRISPR inhibition in a mesenchymal cell line reduced the mesenchymal and basal-like phenotype of the cell line. In summary our study shows that maternally expressed ncRNAs are markers of EMT and suggests that MEG3 is a novel regulator of EMT/MET in breast tissue. Nevertheless, further studies are needed to fully dissect the molecular pathways influenced by non-coding RNAs at the DLK1-DIO3 locus in breast tissue.
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| Overall design |
A total of ten samples were analyzed: Five replicates from D492M KD ctrl and five replicates from D492M KD MEG3. However, sample no. 5 from D492M KD ctrl was omitted due to high deviation from the outher four samples.
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| Contributor(s) |
Budkova Z, Sigurdsson S |
| Citation(s) |
32612992 |
| |
| Submission date |
Dec 18, 2019 |
| Last update date |
Jul 06, 2020 |
| Contact name |
Zuzana Budkova |
| Organization name |
University of Iceland
|
| Department |
BioMedical Center, School of Health Sciences
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| Lab |
Stem Cell Research Unit
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| Street address |
Vatnsmyrarvegi 14
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| City |
Reykjavik |
| ZIP/Postal code |
101 |
| Country |
Iceland |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA596443 |
| SRA |
SRP238079 |
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