Dysregulation of hepatic microRNA expression in C57BL/6 mice affected by excretory-secretory products of Fasciola gigantica

Shi, Wei; He, Jun-Jun; Mei, Xue-Fang; Lu, Ke-Jing; Zeng, Zi-Xuan; Zhang, Yao-Yao; Sheng, Zhao-An; Elsheikha, Hany M.; Huang, Wei-Yi; Zhu, Xing-Quan

Abstract

The excretory-secretory products released by the liver fluke Fasciola gigantica (FgESPs) play important roles in regulating the host immune response during the infection. Identification of hepatic miRNAs altered by FgESPs may improve our understanding of the pathogenesis of F. gigantica infection. In this study, we investigated the alterations in the hepatic microRNAs (miRNAs) in mice treated with FgESPs using high-throughput small RNA (sRNA) sequencing and bioinformatics analysis. The expression of seven miRNAs was confirmed by quantitative stem-loop reverse transcription quantitative PCR (qRT-PCR). A total of 1,313 miRNAs were identified in the liver of mice, and the differentially expressed (DE) miRNAs varied across the time lapsed post exposure to FgESPs. We identified 67, 154 and 53 dysregulated miRNAs at 1, 4 and 12 weeks post-exposure, respectively. 5 miRNAs (miR-126a-3p, miR-150-5p, miR-155-5p, miR-181a-5p and miR-362-3p) were commonly dysregulated at the three time points. We also found that most of the DE miRNAs were induced by FgESPs in the mouse liver after 4 weeks of exposure. These were subjected to Gene Ontology (GO) enrichment analysis, which showed that the predicted targets of the hepatic DE miRNAs of mice 4 weeks of FgESPs injection were enriched in GO terms, including cell membrane, ion binding, cellular communication, organelle and DNA damage. KEGG analysis indicated that the predicted targets of the most downregulated miRNAs were involved in 15 neural activity-related pathways, 6 digestion-related pathways, 20 immune response-related pathways and 17 cancer-related pathways. These data provide new insights into how FgESPs can dysregulate hepatic miRNAs, which play important roles in modulating several aspects of F. gigantica pathogenesis.

Citation

Shi, W., He, J., Mei, X., Lu, K., Zeng, Z., Zhang, Y., …Zhu, X. (2020). Dysregulation of hepatic microRNA expression in C57BL/6 mice affected by excretory-secretory products of Fasciola gigantica. PLoS Neglected Tropical Diseases, 14(12), Article e0008951. https://doi.org/10.1371/journal.pntd.0008951

• Journal Article Type: Article
• Acceptance Date: Nov 3, 2020
• Online Publication Date: Dec 17, 2020
• Publication Date: Dec 1, 2020
• Deposit Date: Dec 19, 2020
• Publicly Available Date: Jan 11, 2021
• Journal: PLoS neglected tropical diseases
• Electronic ISSN: 1935-2735
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 12
• Article Number: e0008951
• DOI: https://doi.org/10.1371/journal.pntd.0008951
• Keywords: Public Health, Environmental and Occupational Health; Infectious Diseases
• Public URL: https://nottingham-repository.worktribe.com/output/5157288
• Publisher URL: https://doi.org/10.1371/journal.pntd.0008951