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

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.

SUBMITTER: Dong X

PROVIDER: S-EPMC4846958 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Dong Xiyuan X Sui Cong C Huang Kai K Wang Lan L Hu Dan D Xiong Ting T Wang Rui R Zhang Hanwang H

American journal of translational research 20160215 2

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 stu ...[more]

PMID: 27158401

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Project description:BackgroundA receptive endometrium is essential for maternal-embryonic molecular communication during implantation. However, the specific molecular regulatory mechanisms of the endometrial capacity remain poorly understood. Here, we examined activating transcription factor 3 (ATF3) expression in human endometria and the functional effect of ATF3 on embryo attachment in vitro.MethodsImmunohistochemistry (IHC) was used to assess the ATF3 expression patterns in human endometria. Quantitative real-time PCR (qRT-PCR), western blotting and immunofluorescence (IF) studies were applied to explore ATF3 expression in Ishikawa cells upon estrogen (E2) and medroxyprogesterone acetate (MPA) treatment. qRT-PCR and western blotting were performed to inspect LIF (leukemia inhibitory factor) expression after enhancement or inhibition of ATF3, and a luciferase reporter assay and ChIP-PCR were used to confirm the regulatory mechanism of ATF3 to LIF. Endometrial epithelial capacity was assessed by an in vitro model of attachment of BeWo spheroids to Ishikawa cells. Western blotting was performed to compare the expression of ATF3 in endometrial samples of recurrent implantation failure (RIF) patients with that in samples from fertile women (FER) who had undergone no less than one successful embryo transplantation.ResultsATF3 was located in human endometrial epithelial cells and stromal cells and was significantly induced by E2 and MPA in Ishikawa cells. Adenovirus-mediated overexpression of ATF3 in Ishikawa cells activated LIF promoter activity and enhanced its expression. Accordingly, the stimulation of BeWo spheroid adhesion promoted by ATF3 was inhibited by pretreatment with a specific antibody against LIF via the antibody-blocking assay. Moreover, ATF3 was aberrantly decreased in the endometria of RIF patients.ConclusionsOur findings suggest that ATF3 plays a significant role in regulating human endometrial receptivity and embryo attachment in vitro via up-regulation of leukemia inhibitory factor.Trial registrationConstruction and management of the Nanjing multi-center biobank. No. 2013-081-01 . Registered 10 Dec. 2013.

Project description:Atherosclerosis is one of the leading causes of mortality worldwide. Growing evidence suggested that miRNAs contributed to the progression of atherosclerosis. miR-30-5p was found involved in various diseases. However, the role of miR-30-5p in regulation of atherosclerosis is not known. Here, we aim to investigate the effects of miR-30-5p on regulating the progression of atherosclerosis. The expression levels of miR-30-5p in serum collected from atherosclerosis patients and normal healthy people were analyzed by qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway bioinformatics were carried out to reveal the possible signaling pathways involved in the mode of action of miR-30-5p. A potential target gene of miRNA-30-5p was searched and examined by a luciferase reporter assay. ELISA, Western blot, proliferation, and flow cytometry assays were performed to assess the biological functional role of miR-30-5p in vitro. Also, an in vitro monocyte-endothelial cell coculture model was used to study the functional role of miR-30-5p in atherosclerosis. We found that miR-30-5p was significantly decreased in serum samples from atherosclerosis patients compared with control subjects. GO and KEGG analysis results showed that miR-30-5p is highly associated with genetic profile of cardiovascular disease. TCF21 was verified as a target gene of miR-30-5p. Overexpression of miR-30-5p in THP-1 not only protected endothelial cell viability but also inhibited endothelial cell apoptosis, and similar results were observed in cells with that of TCF21 knocked down. Moreover, miR-30-5p decreased the expression levels of lactate dehydrogenase (LDH) and tumor necrosis factor-α (TNF-α) and reduced reactive oxygen species (ROS) accumulation. NF-κB and MAPK/p38 pathways played an indispensable role in the protection ability of miR-30-5p against atherosclerosis. Our results reveal that miR-30-5p suppresses the progression of atherosclerosis through targeting TCF21 in vitro. Therefore, the miR-30-5p-TCF21-MAPK/p38 signaling pathway may be a potential biomarker or therapeutic target in atherosclerosis.

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

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

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