A MicroRNA-Mediated Insulin Signaling Pathway Regulates the Toxicity of Multi-Walled Carbon Nanotubes in Nematode Caenorhabditis elegans.

Yunli Zhao,Dayong Wang,Junnian Yang

doi:10.1038/srep23234

Yunli Zhao, Dayong Wang + Show 1 more

Open Access

https://doi.org/10.1038/srep23234

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Journal: Scientific Reports	Publication Date: Mar 17, 2016
Citations: 46	License type: CC BY 4.0

Affiliation: Southeast University

Abstract

The underlying mechanisms for functions of microRNAs (miRNAs) in regulating toxicity of nanomaterials are largely unclear. Using Illumina HiSeqTM 2000 sequencing technique, we obtained the dysregulated mRNA profiling in multi-walled carbon nanotubes (MWCNTs) exposed nematodes. Some dysregulated genes encode insulin signaling pathway. Genetic experiments confirmed the functions of these dysregulated genes in regulating MWCNTs toxicity. In the insulin signaling pathway, DAF-2/insulin receptor regulated MWCNTs toxicity by suppressing function of DAF-16/FOXO transcription factor. Moreover, we raised a miRNAs-mRNAs network involved in the control of MWCNTs toxicity. In this network, mir-355 might regulate MWCNTs toxicity by inhibiting functions of its targeted gene of daf-2, suggesting that mir-355 may regulate functions of the entire insulin signaling pathway by acting as an upregulator of DAF-2, the initiator of insulin signaling pathway, in MWCNTs exposed nematodes. Our results provides highlight on understanding the crucial role of miRNAs in regulating toxicity of nanomaterials in organisms.

Highlights

Previous studies have demonstrated the toxic effects of multi-walled carbon nanotubes (MWCNTs) in inducing oxidative stress, altered immune or inflammatory response, reproductive toxicity, pulmonary toxicity, hepatotoxicology, and/or formation of mesothelioma in mammals[4,6,7,8,9]
We further found that 99.11% of the total reads of transcripts for control group and 99.15% of the total reads of transcripts for MWCNTs exposure group could be mapped among these reads
Among the identified dysregulated genes based on the Illumina HiSeqTM 2000 sequencing data, we found that some genes associated with the control of oxidative stress or intestinal development have been identified previously in MWCNTs exposed nematodes based on quantitative real-time polymerase chain reaction (qRT-PCR) assay[15,19]

Summary

Introduction

Previous studies have demonstrated the toxic effects of MWCNTs in inducing oxidative stress, altered immune or inflammatory response, reproductive toxicity, pulmonary toxicity, hepatotoxicology, and/or formation of mesothelioma in mammals[4,6,7,8,9]. With the aid of the identified miRNAs-mRNAs network involved in the control of MWCNTs toxicity, we examined the underling mechanism for mir-355 in regulating MWCNTs toxicity through influencing the functions of insulin signaling pathways in nematodes.

Results

Conclusion