A regulative epigenetic circuit supervised by HDAC7 represses IGFBP6 and IGFBP7 expression to sustain mammary stemness
| Autor: | Eros Di Giorgio, Vanessa Tolotto, Claudio Brancolini, Valentina Cutano, Martina Minisini, Emiliano Dalla |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Mef2
Cancer Research IGFBP7 retinoids FABP5 Regulator miR-218 Biology Fatty Acid-Binding Proteins Histone Deacetylases Cell Line Epigenesis Genetic stemness Downregulation and upregulation Genetics Gene silencing Humans Epigenetics Insulin-Like Growth Factor I Mammary Glands Human Psychological repression breast Retinoid X Receptor alpha ChIP-seq CRABP2 HDAC7 IGF1 MEF2 Cell biology Insulin-Like Growth Factor Binding Proteins Insulin-Like Growth Factor Binding Protein 6 |
| Popis: | Background: In the breast, the pleiotropic epigenetic regulator HDAC7 can influence stemness. Materials & Methods: The authors used MCF10 cells knocked-out for HDAC7 to explore the contribution of HDAC7 to IGF1 signaling. Results: HDAC7 buffers H3K27ac levels at the IGFBP6 and IGFBP7 genomic loci and influences their expression. In this manner, HDAC7 can tune IGF1 signaling to sustain stemness. In HDAC7 knocked-out cells, RXRA promotes the upregulation of IGFBP6/7 mRNAs. By contrast, HDAC7 increases FABP5 expression, possibly through repression of miR-218. High levels of FABP5 can reduce the delivery of all-trans-retinoic acid to RXRA. Accordingly, the silencing of FABP5 increases IGFBP6 and IGFBP7 expression and reduces mammosphere generation. Conclusion: The authors propose that HDAC7 controls the uptake of all-trans-retinoic acid, thus influencing RXRA activity and IGF1 signaling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|