| First Author | Lu YC | Year | 2012 |
| Journal | Cell Res | Volume | 22 |
| Issue | 10 | Pages | 1453-66 |
| PubMed ID | 22664907 | Mgi Jnum | J:321340 |
| Mgi Id | MGI:6822463 | Doi | 10.1038/cr.2012.88 |
| Citation | Lu YC, et al. (2012) CFTR mediates bicarbonate-dependent activation of miR-125b in preimplantation embryo development. Cell Res 22(10):1453-66 |
| abstractText | Although HCO(3)(-) is known to be required for early embryo development, its exact role remains elusive. Here we report that HCO(3)(-) acts as an environmental cue in regulating miR-125b expression through CFTR-mediated influx during preimplantation embryo development. The results show that the effect of HCO(3)(-) on preimplantation embryo development can be suppressed by interfering the function of a HCO(3)(-)-conducting channel, CFTR, by a specific inhibitor or gene knockout. Removal of extracellular HCO(3)(-) or inhibition of CFTR reduces miR-125b expression in 2 cell-stage mouse embryos. Knockdown of miR-125b mimics the effect of HCO(3)(-) removal and CFTR inhibition, while injection of miR-125b precursor reverses it. Downregulation of miR-125b upregulates p53 cascade in both human and mouse embryos. The activation of miR-125b is shown to be mediated by sAC/PKA-dependent nuclear shuttling of NF-kappaB. These results have revealed a critical role of CFTR in signal transduction linking the environmental HCO(3)(-) to activation of miR-125b during preimplantation embryo development and indicated the importance of ion channels in regulation of miRNAs. |
