title: STAT3-dependent transactivation of miRNA genes following Toxoplasma gondii infection in macrophage.
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.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Cai
authors.forename: He
authors.initials: H
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Yibo
authors.initials: Y
authors.lastname: You
authors.affiliation: Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China. 271313069@qq.com.
authors.forename: Jilong
authors.initials: J
authors.lastname: Shen
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D008264:Macrophages / Q000469:parasitology* / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014122:Toxoplasma / Q000502:physiology*
chemical_list: D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human