Integrated mRNA and micro RNA profiling reveals epigenetic mechanism of differential sensitivity of Jurkat T cells to AgNPs and Ag ions

Hyun Jeong Eom, Nivedita Chatterjee, Jeongsoo Lee, Jinhee Choi

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

•mRNA and micro RNA microarrays revealed more DEGs and DE miRNAs were induced by AgNPs than by Ag ions exposure.•AgNPs-induced MT1F and TRIB3 and Ag ion induced-ENDOGL1 expression was regulated by miR-219-5p and miR 654-3p, respectively.•Network of miR-219-5p-MT1F and -TRIB3 pairs by AgNPs was found to be involved in various cellular processes.•Overall results suggest that distinct epigenetic mechanism is involved in differential toxicity of AgNPs and Ag ions in Jurkat T cells. In our previous in vitro study of the toxicity on silver nanoparticles (AgNPs), we observed a dramatically higher sensitivity of Jurkat T cells to AgNPs than to Ag ions, and DNA damage and apoptosis were found to be involved in that toxicity. In this study, to understand underlying mechanism of different sensitivity of Jurket T cells to AgNPs and Ag ions, mRNA microarray and micro RNA microarray were concomitantly conducted on AgNPs and Ag ions exposed Jurkat T cells. Surprisingly only a small number of genes were differentially expressed by exposure to each of the silver (15 altered mRNA by AgNPs exposure, whereas 4 altered mRNA by Ag ions exposure, as determined 1.5-fold change as the cut-off value). miRNA microarray revealed that the expression of 63 miRNAs was altered by AgNPs exposure, whereas that of 32 miRNAs was altered by Ag ions exposure. An integrated analysis of mRNA and miRNA expression revealed that the expression of hsa-miR-219-5p, was negatively correlated with the expression of metallothionein 1F (MT1F) and tribbles homolog 3 (TRIB3), in cells exposed to AgNPs; whereas, the expression of hsa-miR-654-3p was negatively correlated with the expression of mRNA, endonuclease G-like 1 (EDGL1) in cells exposed to Ag ions. Network analysis were further conducted on mRNA-miRNA pairs, which revealed that miR-219-5p-MT1F and -TRIB3 pairs by AgNPs are being involved in various cellular processes, such as, oxidative stress, cell cycle and apoptosis, whereas, miR-654-3p and ENDOGL1 pair by Ag ions generated a much simpler network. The putative target genes of AgNPs-induced miR-504, miR-33 and miR-302 identified by Tarbase 6.0 are also found to be involved in DNA damage and apoptosis. These results collectively suggest that distinct epigenetic regulation may be an underlying mechanism of different sensitivity of Jurkat T cells to AgNPs and Ag ion. Further identification of putative target genes of DE miRNA by AgNPs and Ag ions may provide additional clues for the mechanism of differential toxicity. Overall results suggest that epigenetic mechanism is involved in toxicity of AgNPs and Ag ions in Jurkat T cells.

Original languageEnglish
Pages (from-to)311-318
Number of pages8
JournalToxicology Letters
Volume229
Issue number1
DOIs
StatePublished - 17 Aug 2014

Keywords

  • Epigenetic mechanism
  • Integrated analysis
  • MiR-219-5p
  • MiR-654-3p
  • Silver nanoparticles

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