Suppression of epithelial-mesenchymal transition and apoptotic pathways by miR-294/302 family synergistically blocks let-7-induced silencing of self-renewal in embryonic stem cells
| Autor: | Scott A. Oakes, Wei Guo, Nichole A. Reyes, Robert Blelloch, Archana Shenoy, Yangming Wang, Wang Xw, Yan Yl, Zhang Q, Yin X, Collin Melton, Ya-Pu Li |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Original Paper
Epithelial-Mesenchymal Transition Cellular differentiation Apoptosis Cell Biology Biology Embryonic stem cell Cell biology Mice MicroRNAs Downregulation and upregulation microRNA Cell Self Renewal embryonic structures Gene silencing Animals Epithelial–mesenchymal transition Molecular Biology Psychological repression Embryonic Stem Cells Signal Transduction |
| Zdroj: | Oakes, Scott; Blelloch, Robert; Guo, WT; Wang, XW; Yan, YL; Li, YP; et al.(2015). Suppression of epithelial-mesenchymal transition and apoptotic pathways by miR-294/302 family synergistically blocks let-7-induced silencing of self-renewal in embryonic stem cells. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/3fg457xt Cell Death and Differentiation |
| Popis: | The embryonic stem cell (ESC)-enriched miR-294/302 family and the somatic cell-enriched let-7 family stabilizes the self-renewing and differentiated cell fates, respectively. The mechanisms underlying these processes remain unknown. Here we show that among many pathways regulated by miR-294/302, the combinatorial suppression of epithelial–mesenchymal transition (EMT) and apoptotic pathways is sufficient in maintaining the self-renewal of ESCs. The silencing of ESC self-renewal by let-7 was accompanied by the upregulation of several EMT regulators and the induction of apoptosis. The ectopic activation of either EMT or apoptotic program is sufficient in silencing ESC self-renewal. However, only combined but not separate suppression of the two programs inhibited the silencing of ESC self-renewal by let-7 and several other differentiation-inducing miRNAs. These findings demonstrate that combined repression of the EMT and apoptotic pathways by miR-294/302 imposes a synergistic barrier to the silencing of ESC self-renewal, supporting a model whereby miRNAs regulate complicated cellular processes through synergistic repression of multiple targets or pathways. |
| Databáze: | OpenAIRE |
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