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  • Title: STAT3-dependent transactivation of miRNA genes following Toxoplasma gondii infection in macrophage.
    Author: Cai Y, Chen H, Jin L, You Y, Shen J.
    Journal: Parasit Vectors; 2013 Dec 16; 6():356. PubMed ID: 24341525.
    Abstract:
    BACKGROUND: The apicomplexan parasite Toxoplasma gondii can infect and replicate in virtually any nucleated cell in many species of warm-blooded animals; T. gondii has elaborate mechanisms to counteract host-cell apoptosis in order to maintain survival and breed in the host cells. METHODS: Using microarray profiling and a combination of conventional molecular approaches, we investigated the levels of microRNAs (miRNAs ) in human macrophage during T. gondii infection. We used molecular tools to examine Toxoplasma-upregualted miRNAs to revealed potential signal transducers and activators of transcription 3(STAT3) binding sites in the promoter elements of a subset of miRNA genes. We analysed the apoptosis of human macrophage with the functional inhibition of the STAT3-binding miRNAs by flow cytometry. RESULTS: Our results demonstrated differential alterations in the mature miRNA expression profile in human macrophage following T. gondii infection. Database analysis of Toxoplasma-upregulated miRNAs revealed potential STAT3 binding sites in the promoter elements of a subset of miRNA genes. We demonstrated that miR-30c-1, miR-125b-2, miR-23b-27b-24-1 and miR-17 ~ 92 cluster genes were transactivated through promoter binding of the STAT3 following T. gondii infection. Importantly, functional inhibition of selected STAT3-binding miRNAs in human macropahges increased apoptosis of host cells. CONCLUSIONS: A panel of miRNAs is regulated through promoter binding of the STAT3 in human macrophage and these miRNAs are involved in anti-apoptosis in response to T. gondii infection.
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