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Altered levels of circulating miRNAs are associated Schistosoma japonicum infection in mice

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...

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Autores principales: Zhu, Lihui, Dao, Jinwei, Du, Xiaoli, Li, Hao, Lu, Ke, Liu, Jinming, Cheng, Guofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391475/
https://www.ncbi.nlm.nih.gov/pubmed/25885182
http://dx.doi.org/10.1186/s13071-015-0806-5
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author Zhu, Lihui
Dao, Jinwei
Du, Xiaoli
Li, Hao
Lu, Ke
Liu, Jinming
Cheng, Guofeng
author_facet Zhu, Lihui
Dao, Jinwei
Du, Xiaoli
Li, Hao
Lu, Ke
Liu, Jinming
Cheng, Guofeng
author_sort Zhu, Lihui
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-0806-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-43914752015-04-10 Altered levels of circulating miRNAs are associated Schistosoma japonicum infection in mice Zhu, Lihui Dao, Jinwei Du, Xiaoli Li, Hao Lu, Ke Liu, Jinming Cheng, Guofeng Parasit Vectors Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-0806-5) contains supplementary material, which is available to authorized users. BioMed Central 2015-04-01 /pmc/articles/PMC4391475/ /pubmed/25885182 http://dx.doi.org/10.1186/s13071-015-0806-5 Text en © Zhu et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zhu, Lihui
Dao, Jinwei
Du, Xiaoli
Li, Hao
Lu, Ke
Liu, Jinming
Cheng, Guofeng
Altered levels of circulating miRNAs are associated Schistosoma japonicum infection in mice
title Altered levels of circulating miRNAs are associated Schistosoma japonicum infection in mice
title_full Altered levels of circulating miRNAs are associated Schistosoma japonicum infection in mice
title_fullStr Altered levels of circulating miRNAs are associated Schistosoma japonicum infection in mice
title_full_unstemmed Altered levels of circulating miRNAs are associated Schistosoma japonicum infection in mice
title_short Altered levels of circulating miRNAs are associated Schistosoma japonicum infection in mice
title_sort altered levels of circulating mirnas are associated schistosoma japonicum infection in mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391475/
https://www.ncbi.nlm.nih.gov/pubmed/25885182
http://dx.doi.org/10.1186/s13071-015-0806-5
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