Abstract

In nematode Caenorhabditis elegans, some microRNAs (miRNAs) could be dysregulated by multi-walled carbon nanotubes (MWCNTs), suggesting their involvement in regulating the response of nematodes to MWCNTs. Among these dysregulated miRNAs induced by MWCNT exposure, prolonged exposure to MWCNTs increased mir-35 expression. mir-35 further acted in the intestine to regulate the response to MWCNTs. In the intestine, a transcription factor MAB-3 was identified as its target in regulating the response to MWCNTs. Moreover, during the control of response to MWCNTs, MAB-3 acted upstream of DAF-16, a fork head transcriptional factor in insulin signaling pathway. Therefore, MWCNTs exposure potentially dysregulates intestinal mir-35 and its direct target MAB-3, which may activate a protective intestinal response of nematodes against the MWCNTs toxicity.

Highlights

  • During the last decades, carbon nanotubes (CNTs) have attracted the great interest for some of their unique properties, such as stability, rigidity, extraordinary tensile strength, and efficient heat conduction[1,2,3]

  • Based on the rescue assays, we found that transgenic expression of neuronal, muscle, or epidermal mir-35 did not obviously affect the susceptibility of mir-35 mutant nematodes to the toxicity of multi-walled carbon nanotubes (MWCNTs) (0.1 μg/L) in inducing intestinal reactive oxygen species (ROS) production (Fig. 1)

  • We observed that prolonged exposure to MWCNTs (≥100 ng/L) could significantly increase the expression of mir-35 (Fig. S1)

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Summary

Introduction

Carbon nanotubes (CNTs) have attracted the great interest for some of their unique properties, such as stability, rigidity, extraordinary tensile strength, and efficient heat conduction[1,2,3]. The underlying molecular mechanisms for the response of organisms to MWCNTs are still largely unclear. The previous studies have demonstrated that some miRNAs could be dysregulated by carbon-based nanomaterials, such as MWCNTs and graphene oxide (GO), and some miRNAs were further shown to be required for the control of toxicity induction of MWCNTs or GO18,19. The underlying mechanism for the role of mir-35 in regulating the response to MWCNTs is still unknown in nematodes. We first examined the tissue-specific activity of mir-35 in regulating the response to MWCNTs. we identified the target of intestinal mir-35 and the underlying www.nature.com/scientificreports/. Mechanism for intestinal mir-35 in regulating the response to MWCNTs. Our results demonstrated that the increase in mir-35 expression mediated a protective intestinal response to MWCNTs by suppressing function of MAB-3-DAF-16 signaling cascade. Our data provides an important molecular basis for intestinal response to MWCNTs in organisms

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