Profiling Non-Coding RNA Changes Associated with 16 Different Engineered Nanomaterials in a Mouse Airway Exposure Model.

Joseph Ndika,Harri Alenius,Pia Kinaret,Marit Ilves,Piia Karisola

doi:10.3390/cells10051085

Joseph Ndika, Harri Alenius + Show 3 more

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https://doi.org/10.3390/cells10051085

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Abstract

Perturbations in cellular molecular events and their associated biological processes provide opportunities for hazard assessment based on toxicogenomic profiling. Long non-coding RNAs (lncRNAs) are transcribed from DNA but are typically not translated into full-length proteins. Via epigenetic regulation, they play important roles in organismal response to environmental stress. The effects of nanoparticles on this important part of the epigenome are understudied. In this study, we investigated changes in lncRNA associated with hazardous inhalatory exposure of mice to 16 engineered nanomaterials (ENM)–4 ENM (copper oxide, multi-walled carbon nanotubes, spherical titanium dioxide, and rod-like titanium dioxide particles) with 4 different surface chemistries (pristine, COOH, NH2, and PEG). Mice were exposed to 10 µg of ENM by oropharyngeal aspiration for 4 consecutive days, followed by cytological analyses and transcriptomic characterization of whole lung tissues. The number of significantly altered non-coding RNA transcripts, suggestive of their degrees of toxicity, was different for each ENM type. Particle surface chemistry and shape also had varying effects on lncRNA expression. NH2 and PEG caused the strongest and weakest responses, respectively. Via correlational analyses to mRNA expression from the same samples, we could deduce that significantly altered lncRNAs are potential regulators of genes involved in mitotic cell division and DNA damage response. This study sheds more light on epigenetic mechanisms of ENM toxicity and also emphasizes the importance of the lncRNA superfamily as toxicogenomic markers of adverse ENM exposure.

Highlights

Introduction published maps and institutional affilDue to their ongoing contributions to sustainable nanotechnology-based innovations, engineered nanomaterials (ENM) are still being produced in bulk quantities worldwide [1].Workers and consumers continuously come in contact with a diverse array of potentially hazardous substances
The immunomodulatory effects of CuO and multiwalled carbon nanotubes (MWCNT) appear to be primarily mediated via Long non-coding RNAs (lncRNAs)-independent mechanisms, whereas in TiO2 p exposures, a subset of lncRNA-regulated DEG that are involved in immune cell migration were identified
The fact that the expression of lncRNA transcripts from lncRNA-mRNA co-regulated networks of DNA damage and repair response pathways, clusters the different ENM according to their cytotoxic potential, emphasizes the biological relevance of lncRNA expression profiling in toxicogenomic studies

Summary

Introduction

Introduction published maps and institutional affilDue to their ongoing contributions to sustainable nanotechnology-based innovations, engineered nanomaterials (ENM) are still being produced in bulk quantities worldwide [1].Workers and consumers continuously come in contact with a diverse array of potentially hazardous substances. Due to their ongoing contributions to sustainable nanotechnology-based innovations, engineered nanomaterials (ENM) are still being produced in bulk quantities worldwide [1]. Biological toxicity of ENM depends on the size and shape of the core material and on the used surface chemistry. Carboxylation (-COOH) and especially polyethylene glycosylation (PEG) are often shown to reduce bioactivity and pathogenicity of ENM, while amination (-NR3 + ) is sometimes reported to even enhance toxicity of the same particles when compared to its pristine (unmodified or core) form [2,3,4,5]. We have recently shown that core material chemistry and surface modifications of these 16, and 12 other iations

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