Volume 22, No 10, Oct 2012
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 22 Issue 10, October 2012: 1453-1466
ORIGINAL ARTICLES
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,
1The Chinese University of Hong Kong ?Zhejiang University Joint Laboratory for Human Reproduction and Related Diseases
2Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
3Department of Reproductive Endocrinology, Key Laboratory of Reproductive Genetics of Ministry of Education of China, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China
4Key Laboratory for Regenerative Medicine (Jinan University ?The Chinese University of Hong Kong), Ministry of Education of China, Guangzhou, Guangdong 510632, China
5Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
6Henan Institute of Population and Family Planning Research, Zhengzhou, Henan 450000, China
7Sichuan University ?The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, Women and Children's Hospital, Sichuan University, Chengdu, Sichuan 610041, China
Correspondence: Hsiao Chang Chan, He Feng Huang,(hsiaocchan@cuhk.edu.hk; huanghefg@hotmail.com)
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.
Cell Research (2012) 22:1453-1466. doi:10.1038/cr.2012.88; published online 5 June 2012
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