Comprehensive Analysis of SiNPs on the Genome-Wide Transcriptional Changes in Caenorhabditis elegans

Int J Nanomedicine. 2020 Jul 23:15:5227-5237. doi: 10.2147/IJN.S251269. eCollection 2020.

Abstract

Background: Large-scale production and application of amorphous silica nanoparticles (SiNPs) have enhanced the risk of human exposure to SiNPs. However, the toxic effects and the underlying biological mechanisms of SiNPs on Caenorhabditis elegans remain largely unclear.

Purpose: This study was to investigate the genome-wide transcriptional alteration of SiNPs on C. elegans.

Methods and results: In this study, a total number of 3105 differentially expressed genes were identified in C. elegans. Among them, 1398 genes were significantly upregulated and 1707 genes were notably downregulated in C. elegans. Gene ontology analysis revealed that the significant change of gene functional categories triggered by SiNPs was focused on locomotion, determination of adult lifespan, reproduction, body morphogenesis, multicellular organism development, endoplasmic reticulum unfolded protein response, oocyte development, and nematode larval development. Meanwhile, we explored the regulated effects between microRNA and genes or signaling pathways. Pathway enrichment analysis and miRNA-gene-pathway-network displayed that 23 differential expression microRNA including cel-miR-85-3p, cel-miR-793, cel-miR-241-5p, and cel-miR-5549-5p could regulate the longevity-related pathways and inflammation signaling pathways, etc. Additionally, our data confirmed that SiNPs could disrupt the locomotion behavior and reduce the longevity by activating ins-7, daf-16, ftt-2, fat-5, and rho-1 genes in C. elegans.

Conclusion: Our study showed that SiNPs induced the change of the whole transcriptome in C. elegans, and triggered negative effects on longevity, development, reproduction, and body morphogenesis. These data provide abundant clues to understand the molecular mechanisms of SiNPs in C. elegans.

Keywords: development; Caenorhabditis elegans; SiNPs; genome microarrays; longevity.

MeSH terms

  • Animals
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / genetics
  • Gene Expression Regulation / drug effects*
  • Gene Regulatory Networks / drug effects
  • Genome, Helminth
  • Humans
  • Longevity / drug effects
  • MicroRNAs / genetics
  • Mutagenicity Tests / methods
  • Nanoparticles / chemistry
  • Nanoparticles / toxicity*
  • Reproduction / drug effects
  • Signal Transduction / drug effects
  • Silicon Dioxide / chemistry
  • Silicon Dioxide / toxicity
  • Transcriptome
  • Unfolded Protein Response / genetics

Substances

  • Caenorhabditis elegans Proteins
  • MicroRNAs
  • Silicon Dioxide