MicroRNA-223-3p suppresses leukemia inhibitory factor expression and pinopodes formation during embryo implantation in mice.

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Abstract
MicroRNA (miRNA) regulates gene expression in a post-transcriptional manner, which hybridizes the target mRNAs with complementary sequence and subsequently leads to translation repression or mRNA degradation. Online sequence alignment showed that there is a putative binding site of miR-223-3p on the 3'UTR of LIF, which is considered to be an important marker of endometrial receptivity. Thus, we hypothesized that miR-223-3p may affect embryo implantation by suppressing LIF expression. In this study, we found that miR-223-3p and LIF protein was inversely expressed in the endometrium of mice during implantation window. Then we proved that miR-223-3p directly binds to LIF 3'UTR with luciferase reporter assay and supresses the expression of LIF. To investigate whether miR-233-3p affects embryo implantation, miR-223-3p agonist was injected into the uteri of pregnant mice. The results demonstrated the suppressing effect of miR-223-3p on embryo implantation. Furthermore, over-expression of miR-223-3p was found to compromise pinopodes formation in the endometrium of mice. Taken all together, our findings revealed that miR-223-3p suppresses pinopodes formation and LIF protein expression, which may lead to diminished embryo implantation.

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