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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-06-05

AUTHORS

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

ABSTRACT

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. More... »

PAGES

1453-1466

Journal

TITLE

Cell Research

ISSUE

10

VOLUME

22

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cr.2012.88

DOI

http://dx.doi.org/10.1038/cr.2012.88

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033993911

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22664907


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