6月5日，Cell Res.雜志在線報道了離子通道蛋白通過調(diào)節(jié)HCO3-跨膜運輸,，調(diào)節(jié)miR-125b進(jìn)而調(diào)控胚胎發(fā)育的重要進(jìn)展,。盡管已知HCO3-是早期胚胎發(fā)育所必須的，其確切機(jī)制尚不明了,。
囊性纖維化跨膜傳導(dǎo)調(diào)節(jié)因子(CFTR)可作為HCO3-的跨膜通道,。研究發(fā)現(xiàn)，在著床前胚胎發(fā)育過程中,，通過CFTR介導(dǎo)的HCO3-涌入細(xì)胞,，HCO3-可作為環(huán)境信息調(diào)節(jié)miR-125b的表達(dá)。實驗結(jié)果顯示,，通過施加特異性CFTR抑制因子或敲除CFTR基因,，能抑制HCO3-在著床前胚胎發(fā)育過程中的這一調(diào)節(jié)作用。而注射miR-125b前提可逆轉(zhuǎn)這一效應(yīng),。
在人類及小鼠胚胎中,，下調(diào)miR-125b可上調(diào)p53信號通路級聯(lián)反應(yīng)。miR-125b的激活有賴于sAC/PKA依賴的NF-κB核轉(zhuǎn)運,。這些研究結(jié)果揭示,，CFTR在聯(lián)系著床前胚胎微環(huán)境中HCO3-與miR-125b活化的信號轉(zhuǎn)導(dǎo)過程中發(fā)揮重要作用,。這項研究還證實，離子通道在調(diào)節(jié)miRNA過程中可發(fā)揮重要作用,。（生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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PMID:
CFTR mediates bicarbonate-dependent activation of miR-125b in preimplantation embryo development
Yong Chao Lu1,2,3,6,*, Hui Chen1,2,*, Kin Lam Fok1,2,*, Lai Ling Tsang1,2, Mei Kuen Yu1,2, Xiao Hu Zhang1,2, Jing Chen1,2, Xiaohua Jiang1,2,4, Yiu Wa Chung1,2, Alvin Chun Hang Ma5, Anskar Yu Hung Leung5, He Feng Huang1,3 and Hsiao Chang Chan1,2,4,7
Although HCO3? is known to be required for early embryo development, its exact role remains elusive. Here we report that HCO3? 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 HCO3? on preimplantation embryo development can be suppressed by interfering the function of a HCO3?-conducting channel, CFTR, by a specific inhibitor or gene knockout. Removal of extracellular HCO3? or inhibition of CFTR reduces miR-125b expression in 2 cell-stage mouse embryos. Knockdown of miR-125b mimics the effect of HCO3? 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-κB. These results have revealed a critical role of CFTR in signal transduction linking the environmental HCO3? to activation of miR-125b during preimplantation embryo development and indicated the importance of ion channels in regulation of miRNAs.
