Microarray analysis of long non-coding RNA expression profiles in monocytic myeloid-derived suppressor cells in Echinococcus granulosus-infected mice

Parasit Vectors. 2018 May 30;11(1):327. doi: 10.1186/s13071-018-2905-6.

Abstract

Background: Cystic echinococcosis is a worldwide chronic zoonotic disease caused by infection with the larval stage of Echinococcus granulosus. Previously, we found significant accumulation of myeloid-derived suppressor cells (MDSCs) in E. granulosus infection mouse models and that they play a key role in immunosuppressing T lymphocytes. Here, we compared the long non-coding RNA (lncRNA) and mRNA expression patterns between the splenic monocytic MDSCs (M-MDSCs) of E. granulosus protoscoleces-infected mice and normal mice using microarray analysis.

Methods: LncRNA functions were predicted using Gene Ontology enrichment and the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Cis- and trans-regulation analyses revealed potential relationships between the lncRNAs and their target genes or related transcription factors.

Results: We found that 649 lncRNAs were differentially expressed (fold change ≥ 2, P < 0.05): 582 lncRNAs were upregulated and 67 lncRNAs were downregulated; respectively, 28 upregulated mRNAs and 1043 downregulated mRNAs were differentially expressed. The microarray data was validated by quantitative reverse transcription-PCR. The results indicated that mRNAs co-expressed with the lncRNAs are mainly involved in regulating the actin cytoskeleton, Salmonella infection, leishmaniasis, and the vascular endothelial growth factor (VEGF) signaling pathway. The lncRNA NONMMUT021591 was predicted to cis-regulate the retinoblastoma gene (Rb1), whose expression is associated with abnormal M-MDSCs differentiation. We found that 372 lncRNAs were predicted to interact with 60 transcription factors; among these, C/EBPβ (CCAAT/enhancer binding protein beta) was previously demonstrated to be a transcription factor of MDSCs.

Conclusions: Our study identified dysregulated lncRNAs in the M-MDSCs of E. granulosus infection mouse models; they might be involved in M-MDSC-derived immunosuppression in related diseases.

Keywords: Echinococcus granulosus; Expression profile; Long non-coding RNAs; Microarray analysis; Myeloid-derived suppressor cells.

MeSH terms

  • Animals
  • Down-Regulation
  • Echinococcosis / parasitology*
  • Echinococcus granulosus / genetics*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Microarray Analysis
  • Monocytes / parasitology
  • Myeloid-Derived Suppressor Cells / parasitology
  • RNA, Helminth / genetics
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics*
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / genetics
  • Zoonoses

Substances

  • RNA, Helminth
  • RNA, Long Noncoding
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A