title: Altered levels of circulating miRNAs are associated Schistosoma japonicum infection in mice.
abstract: BACKGROUND
  Dioecious flatworms of the genus Schistosoma causes schistosomiasis, which is a major public health problem in developing countries. Acquiring detailed knowledge of schistosome-host interactions may aid in the development of novel strategies for schistosomiasis control. MicroRNAs (miRNAs) are involved in processes such as development, cell proliferation, metabolism, and signal transduction. Circulating miRNAs not only serve as a novel class of biomarkers of many diseases but also regulate target gene expression in recipient cells, which are similar to hormones.
  
  
  METHODS
  In the present study, we used miRNA microarrays to determine the profile of circulating miRNAs associated with S. japonicum infection of mice. The biological functions of the altered levels of miRNAs and their target genes were predicted using bioinformatics. Expression levels of selected miRNAs and their target genes were further analyzed by quantitative RT-PCR.
  
  
  RESULTS
  Our study identified 294 and 189 miRNAs in infected mice that were expressed in two independent experiments at levels ≥ 2-fold higher or ≤ 0.5-fold lower, respectively, compared with uninfected mice. Thirty-six of the same miRNAs were detected in these analyses. Moreover, pathway analyses indicated that most of these miRNAs are putatively involved in signaling pathways associated with pathogenesis, such as Wnt and MAPK signaling. Further, we show an inverse correlation between the circulating levels of these miRNAs and their target genes, suggesting that changes in miRNA expression may cause aberrant expression of genes such as Creb1 and Caspase-3 in mice infected with S. japonicum.
  
  
  CONCLUSIONS
  Our study shows significant differences in the levels of circulating miRNAs between S. japonicum infected mice and uninfected mice. In particular, the altered levels of miR-706 and miR-134-5p were associated with altered levels of expression of the Caspase-3 and Creb1 genes, respectively, suggesting that circulating miRNAs may serve as important mediators of the pathology of hepatic schistosomiasis. Additionally, our results are expected to provide new insights for further understanding the mechanisms of schistosome-host interaction that may facilitate in the development of novel interventions for alleviating the symptom of S. japonicum infection as well as for preventing and treating schistosomiasis.
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences; Key Laboratory of Animal Parasitology, Ministry of Agriculture, 518 Ziyue Road, Shanghai, China. zhulihui@shvri.ac.cn.
authors.forename: Lihui
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences; Key Laboratory of Animal Parasitology, Ministry of Agriculture, 518 Ziyue Road, Shanghai, China. khunfa1905@hotmail.com.
authors.forename: Jinwei
authors.initials: J
authors.lastname: Dao
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences; Key Laboratory of Animal Parasitology, Ministry of Agriculture, 518 Ziyue Road, Shanghai, China. du_xiaoli_2008@163.com.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Du
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences; Key Laboratory of Animal Parasitology, Ministry of Agriculture, 518 Ziyue Road, Shanghai, China. lihao@shvri.ac.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences; Key Laboratory of Animal Parasitology, Ministry of Agriculture, 518 Ziyue Road, Shanghai, China. luke@shvri.ac.cn.
authors.forename: Ke
authors.initials: K
authors.lastname: Lu
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences; Key Laboratory of Animal Parasitology, Ministry of Agriculture, 518 Ziyue Road, Shanghai, China. jimyliu@shvri.ac.cn.
authors.forename: Jinming
authors.initials: J
authors.lastname: Liu
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences; Key Laboratory of Animal Parasitology, Ministry of Agriculture, 518 Ziyue Road, Shanghai, China. cheng_guofeng@yahoo.com.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000818:Animals; D019295:Computational Biology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D051379:Mice; D035683:MicroRNAs / Q000097:blood*; D046228:Microarray Analysis; D060888:Real-Time Polymerase Chain Reaction; D012554:Schistosomiasis japonica / Q000473:pathology*
chemical_list: D035683:MicroRNAs