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miRNA-181 regulates embryo implantation in mice through targeting leukemia inhibitory factor Free
Bo Chu1,†, Liangwen Zhong1,†, Shuang Dou1, Jun Wang1, Jianmin Li2, Mingwei Wang3, Qinghua Shi1,*, Yide Mei1,*, and Mian Wu1,*
1CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei 230027, China
2Department of Cell Biology, Nanjing Medical University, Nanjing 210029, China
3Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China *Correspondence to:Qinghua Shi, E-mail:; Yide Mei, E-mail:; Mian Wu, E-mail:
J Mol Cell Biol, Volume 7, Issue 1, February 2015, Pages 12-22
Keyword: miR-181, LIF, Emx2, embryo implantation

Embryo implantation is a crucial step in mammalian reproduction. However, little is known regarding the physiological roles of microRNAs in the regulation of embryo implantation. Here we show that a minimum uterine expression of miR-181 is essential for the onset of embryo implantation. Both transient and prolonged transgenic expression of miR-181 led to impaired implantation, which can be rescued by exogenous administration of leukemia inhibitory factor (LIF). Mechanistically, miR-181 is able to directly target LIF and downregulate LIF expression, thereby inhibiting embryo implantation. We also show that miR-181 expression is regulated by the transcriptional factor Emx2, and the Emx2–miR-181 axis plays an important role in regulating embryo implantation. Taken together, these results reveal a novel function of miR-181 in embryo implantation through the regulation of LIF, and also indicate a potential link between miR-181 dysregulation and human embryo implantation defects.