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| Status |
Public on Jun 07, 2019 |
| Title |
Sequence diverse miRNAs converge to induce mesenchymal-to-epithelial transition in ovarian cancer cells through direct and indirect regulatory controls |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) are reciprocal molecular processes essential in early embryonic development that have been co-opted by cancer cells to facilitate tumor metastasis. Recent studies have demonstrated that both EMT and MET can be induced by modulations in cellular levels of microRNAs (miRNAs), a well-studied class of small regulatory RNAs. Our laboratory has been particularly interested in the ability of members of the sequentially homologous miR-200 family of miRNAs to induce MET when ectopically over-expressed in mesenchymal-like ovarian cancer (OC) cells. Given that even a single nucleotide substitution within the highly conserved seed region of miRNAs can dramatically change the spectrum of regulated mRNA targets, it is remarkable that families of miRNAs sequentially divergent from one another can similarly regulate the EMT/MET process in a diversity of cancer cells. For example, miR-205, although sequentially highly divergent from members of the miR-200 family, has been reported to display a similar ability to induce MET in mesenchymal-like lung, prostate cancer cells. We report here that although miR-205 has little to no sequence homology with members of the miR-200 family of miRNAs, it induces morphological transitions in mesenchymal OC cells that are morphologically indistinguishable from those induced by members of the sequentially divergent miR-200 family.
We present evidence that the vast majority of the molecular changes underlying these morphological transitions are not brought about by the direct targeting of the same suite of genes but rather by indirect regulatory changes that converge to generate a similar molecular phenotype.
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| Overall design |
Ovarian cancer HEY cells were transfected with miR-200 and miR-205 for 48 hrs. After transfection, RNA were extracted and microarray gene expression analysises were conducted.
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| Contributor(s) |
Zhang M, Jabbari N, Satpathy M, Matyunina LV, Wang Y, McDonald LD, McDonald JF |
| Citation(s) |
31163194 |
| Submission date |
May 02, 2018 |
| Last update date |
Sep 07, 2019 |
| Contact name |
Mengnan Zhang |
| Organization name |
Georgia Institute of Technology
|
| Department |
School of Biological Sciences
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| Lab |
McDonald Lab
|
| Street address |
315 Ferst Drive
|
| City |
Atlanta |
| State/province |
Georgia |
| ZIP/Postal code |
30332 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (20)
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| GSM3124990 |
HEY cells transfected with miR-141-rep1 |
| GSM3124991 |
HEY cells transfected with miR-141-rep2 |
| GSM3124992 |
HEY cells transfected with miR-141-rep3 |
| GSM3124993 |
HEY cells transfected with miR-200b-rep1 |
| GSM3124994 |
HEY cells transfected with miR-200b-rep2 |
| GSM3124995 |
HEY cells transfected with miR-200b-rep3 |
| GSM3124996 |
HEY cells transfected with miR-205-rep1 |
| GSM3124997 |
HEY cells transfected with miR-205-rep2 |
| GSM3124998 |
HEY cells transfected with miR-205-rep3 |
| GSM3426630 |
HEY cells transfected with si-NC-rep1 |
| GSM3426631 |
HEY cells transfected with si-NC-rep2 |
| GSM3426632 |
HEY cells transfected with si-ZEB1-rep1 |
| GSM3426633 |
HEY cells transfected with si-ZEB1-rep2 |
| GSM3426634 |
HEY cells transfected with si-WNT5A-rep1 |
| GSM3426635 |
HEY cells transfected with si-WNT5A-rep2 |
| GSM3426636 |
HEY cells transfected with si-ZEB1-WNT5A-rep1 |
| GSM3426637 |
HEY cells transfected with si-ZEB1-WNT5A-rep2 |
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| Relations |
| BioProject |
PRJNA454705 |
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