CFTR mediates bicarbonate-dependent activation of miR-125b in preimplantation embryo development

Yong Chao Lu, Hui Chen, Kin Lam Fok, Lai Ling Tsang, Mei Kuen Yu, Xiao Hu Zhang, Jing Chen, Xiaohua Jiang, Yiu Wa Chung, Chun Hang Ma, Anskar Yu Hung Leung, He Feng Huang, Hsiao Chang Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

28 Citations (Scopus)

Abstract

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-κB. 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.
Original languageEnglish
Pages (from-to)1453-1466
Number of pages14
JournalCell Research
Volume22
Issue number10
DOIs
Publication statusPublished - 1 Oct 2012
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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